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Biomedical subjects

K R Lee

Publications and source records attributed to K R Lee.

At least 73 records · Page 4Linked to original sources

Adenocarcinoma in situ in cervical smears with a small cell (endometrioid) pattern: distinction from cells directly sampled from the upper endocervical canal or lower segment of the endometrium.

Adenocarcinoma in situ (AIS) with small, endometrioid cells in cervicovaginal smears, is a source of false-negative diagnoses because of the difficulty in distinguishing these cells from endometrial cells of the lower uterine segment or benign cells from the upper endocervical canal. This study was designed to elucidate the most useful criteria for this distinction. Three observers blinded to the actual diagnoses reviewed 29 preselected cases (AIS, 17; benign, 12) that had originally caused diagnostic difficulty. Each observer made a diagnosis and evaluated 15 preselected diagnostic criteria. All 3 observers agreed on the correct diagnosis in 19 (66%) of 29 cases, and at least 2 observers agreed on the correct diagnosis in 27 (93%) of 29 cases. No case was misdiagnosed by all 3 observers. The most useful criteria for the diagnosis of AIS are a predominance of groups with marked crowding, focal feathering, nuclear hyperchromatism with coarsening of chromatin, and occasional mitotic figures. Sheets of cells, endometrial tubules, and endometrial stroma favor a benign diagnosis. Although 12 (14%) of 87 possible diagnoses were erroneous, well-preserved, small, endometrioid AIS cells can be identified correctly on cervical smears and distinguished from epithelium from the lower uterine segment and high endocervical canal in most cases using the aforementioned criteria.

Adenocarcinoma↗

Comparison of microparticle enzyme and fluorescence polarization immunoassays in pediatric patients not receiving digoxin.

Previously, investigators have measured endogenous digoxin-like immunoreactive substances (DLIS) in pediatric patients. Digoxin-like immunoreactive substances may cross-react with digoxin assays to produce false-positive digoxin concentrations; hence, the validity of digoxin concentrations in pediatric patients is questionable. The authors compared the presence and magnitude of apparent DLIS using the microparticle enzyme immunoassay (MEIA) AxSYM Digoxin II and the fluorescence polarization immunoassay (FPIA) TDx Digoxin II, in the serum of 80 pediatric patients who were hospitalized with normal serum creatinine but had not been administered digoxin. Patients ranged in age from 1 day to 16 years (mean age, 4.96 +/- 5.17 years). Serum creatinine and total bilirubin were 0.5 +/- 0.18 mg/dl and 1.3 +/- 0.17 mg/dl, respectively. Forty-eight percent of MEIA samples and 79% of FPIA samples had measurable DLIS values. Digoxin-like immunoreactive substance concentrations for the MEIA (0.07 +/- 0.09 ng/ml) and FPIA assays (0.1 +/- 0.1 ng/ml) were statistically different (p = 0.01); however, no sample had a DLIS value >0.38 ng/ml. A poor correlation was noted between patient age, serum creatinine, total bilirubin, and DLIS concentration. The MEIA and FPIA assays effectively minimized DLIS cross-reactivity making both technologies clinically acceptable for serum digoxin measurement in pediatric patients with normal serum creatinine and total bilirubin.

Adolescent↗

Qualifying the cytologic diagnosis of "atypical squamous cells of undetermined significance" affects the predictive value of a squamous intraepithelial lesion on subsequent biopsy.

OBJECTIVE: To evaluate whether different qualifications of a cytologic diagnosis of "atypical squamous cells of undetermined significance" predict a greater or lesser likelihood of cervical pathology. DESIGN: Comparison of different cytologic qualifications of atypical squamous cells of undetermined significance with the frequency of significant cervical disease as documented by tissue biopsy. PARTICIPANTS AND SETTING: Four hundred, fifty-two consecutive Papanicolaou smears showing atypical squamous cells of undetermined significance (diagnosed by nine cytopathologists) in women who had undergone cervical biopsy within the previous 90 days at Brigham and Women's Hospital, Boston, Mass (January-June 1995). MAIN OUTCOME MEASURE: The histopathologic diagnosis of squamous intraepithelial lesion of the cervix. RESULTS: The 452 smears were qualified as "favor reactive" (22%), "not otherwise specified" (42%), "favor squamous intraepithelial lesion" (29%), and "favor high-grade squamous intraepithelial lesion" (6%). High-grade squamous intraepithelial lesions and total squamous intraepithelial lesions were pathologically confirmed by cervical biopsy in 3.6% and 6% of the favor reactive smears, in 11% and 21% of the not otherwise specified smears, in 12% and 30% of the favor squamous intraepithelial lesion smears, and in 53% and 59% of the favor high-grade squamous intraepithelial lesion smears. Significant associations were seen between a favor reactive smear and a benign finding on cervical biopsy (94%, P = .04) and between a favor high-grade squamous intraepithelial lesion smear and a biopsy that showed a high-grade squamous intraepithelial lesion (53%, P = .00001). CONCLUSIONS: Qualifying atypical squamous cells of undetermined significance stratifies women into different risk groups for squamous intraepithelial lesion. It is reasonable for physicians to make patient management decisions based, at least in part, on such qualifications.

Biopsy↗

Performance of liquid-based, thin-layer cervical cytology: correlation with reference diagnoses and human papillomavirus testing.

The performance of thin-layer cervical cytology with the use of ThinPrep (Cytyc Corporation, Boxborough, MA) was assessed by comparing the original independent diagnosis of ThinPrep slides and conventional smears prepared from 1780 split samples with the most abnormal diagnosis per patient on the basis of an independent pathologist's masked review and with the detection of cancer-associated types of human papillomavirus (HPV) DNA. Cases were selected on the basis of the original diagnoses to include all discordant pairs (those diagnosed as atypical squamous cells of undetermined significance or higher grade, n = 1017), all concordant abnormal pairs (n = 444), and a random 5% of concordant normal pairs (n = 319). In screening centers, thin-layer cytology detected 135 (70.3%) of 192 women diagnosed as having squamous epithelial lesions or a higher grade in the independent review, whereas locally read smears detected 91 (47.4%) of these patients (P < .001). In hospital-based cytology laboratories, thin-layer cytology detected 308 (86.3%) of 357 women diagnosed with SILs or a higher grade in the independent review, compared with 283 (79.3%) diagnosed with smears (P = .011). Cancer-associated types of HPV DNA were detected in a slightly higher proportion of women with smears diagnosed as SILs than in women with thin-layer cytology diagnosed as SILs, whereas the overall number of HPV-associated SILs diagnosed was higher with thin-layer cytology. These data suggest that the ThinPrep method detects a higher percentage of SILs as defined in a masked, independent review than do concurrently prepared smears and that diagnoses of SILs rendered with ThinPrep correlate with the detection of cancer-associated types of HPV.

Cytological Techniques↗

Use of statistical analysis of cytologic interpretation to determine the causes of interobserver disagreement and in quality improvement.

BACKGROUND: Disagreements in cytologic interpretation can have several causes, including differences in diagnostic threshold and diagnostic accuracy. These can be distinguished by a combination of statistical analyses. METHODS: For demonstration purposes, a nonrandom collection of 80 cervicovaginal smears, the majority of which (74) were originally diagnosed as atypical cells of undetermined significance (ASCUS), were reviewed by 3 separate observers and classified as either negative, negative and reactive, ASCUS favor reactive, ASCUS not otherwise specified, ASCUS suggestive of a squamous intraepithelial lesion (SIL), low grade SIL, or high grade SIL. The results were compared with corresponding biopsies and analyzed with distribution analysis, the kappa statistic, threshold analysis, and receiver operating characteristic (ROC) curve analysis. RESULTS: Distribution analysis of diagnoses from the three observers demonstrated statistically significant differences in how cases were classified and a low level of agreement. Kappa analysis confirmed a very poor interobserver agreement. Threshold analysis revealed that one observer used a threshold between negative and ASCUS that was statistically more specific but less sensitive than the other observers. ROC curve analysis showed that another observer was more accurate than this observer. CONCLUSIONS: Variation in cytologic interpretation may have several causes. Distribution, threshold, and ROC analysis allow distinction between differences in diagnostic accuracy and diagnostic thresholds. This approach to analyzing cytologic interpretation may be useful for quality improvement efforts.

Cytological Techniques↗

Koilocytotic atypia in Papanicolaou smears. Reproducibility and biopsy correlations.

BACKGROUND: It would be useful if cervical smears containing koilocytes alone could be reliably separated from those containing other forms of nuclear atypia within the spectrum of low grade squamous intraepithelial lesions (LSIL) and that this separation was predictive of differences in biopsy follow-up. In this article, the authors sought to test this possibility. METHODS: Consecutive smears diagnosed as LSIL from 140 patients who had follow-up colposcopic biopsies were reviewed independently by three observers. The inter- and intraobserver reproducibility in diagnosing smears with koilocytes alone was assessed by the kappa statistic. Comparison of each reviewer's cytologic diagnosis with a reviewed biopsy diagnosis was assessed using chi-square analysis. The quantity of abnormal cells was compared with the presence or absence of a lesion on biopsy. RESULTS: Kappa values for any 2 observers agreeing on koilocytosis as a separate category ranged from 0.22-0.47 (poor to good). Intraobserver reproducibility across all cytologic categories ranged from 0.35-0.62 (poor to good). A cytologic diagnosis of koilocytosis predicted a lower rate of high grade SIL (HSIL) on initial biopsy for one of the observers, but not for the other two. Koilocytosis did not predict a lower rate of LSIL on initial biopsy or HSIL in follow-up biopsies for any observer. The quantity of cells on the initial smear did not correlate with a lesion on biopsy. CONCLUSIONS: Separation of LSIL into two diagnostic categories is not feasible because of its poor cytologic reproducibility and inability to predict differences in biopsy diagnosis. The quantity of abnormal cells in LSIL is not predictive of the detection of a lesion on biopsy.

Biopsy↗

Comparison of conventional Papanicolaou smears and a fluid-based, thin-layer system for cervical cancer screening.

OBJECTIVE: To compare the cytologic diagnoses and specimen adequacy of a fluid-based, thin-layer preparation and conventional Papanicolaou tests. METHODS: A total of 7360 women from six separate sites-three screening centers and three hospitals-participated in split-sample/matched-pair, double-masked clinical trials. A conventional Papanicolaou test was performed, after which residual material on the sampling device was rinsed into a fluid preservative from which a thin-layer slide (ThinPrep) was prepared using the ThinPrep 2000 automated slide processor (Cytyc Corp., Boxborough, MA). Conventional and ThinPrep slides were read independently. Cytologic diagnoses and specimen adequacy were classified using the Bethesda system. RESULTS: For the three screening centers, 65% more diagnoses of low-grade squamous intraepithelial lesions and higher were made on the ThinPrep slides (P < .001); for the three hospital centers, 6% more of these diagnoses were made with the ThinPrep method (P = .294). Comparison of specimen adequacy showed a significant increase in satisfactory specimens and a reduction in the number of "satisfactory but limited by" specimens using the ThinPrep method (P < .001). CONCLUSION: The fluid-based, ThinPrep method of sample preparation resulted in a statistically significant increase in cytologic diagnosis of cervical cancer precursors and in specimen adequacy compared with the conventional Papanicolaou testing method.

Adult↗

Four new cytotoxic germacranolides from Carpesium divaricatum.

In a bioassay-guided search for cytotoxic compounds from higher plants of South Korea, four new sesquiterpenes of the germacranolide type, named cardivins A (1), B (2), C (3), and D (4), have been isolated from the aerial parts of Carpesium divaricatum. Structures of these compounds were elucidated on the basis of spectroscopic techniques. Compounds 1, 2, 3, and 4 showed cytotoxicity to the human tumor cells, A-549 (nonsmall cell lung), SK-OV-3 (ovary), SK-MEL-2 (skin), XF-498 (central nervous system), and HCT-15 (colon).

Antineoplastic Agents, Phytogenic↗

Artekeiskeanin A: a new coumarin-monoterpene ether from Artemisia keiskeana.

A new coumarin-monoterpene ether, artekeiskeanin A (1) and two known coumarins, dracunculin (2) and scopoletin (3) were isolated from the aerial parts of Artemisia keiskeana. The structure of 1 was determined to be 7-(trans-8-oxogeranyloxy)-6-methoxycoumarin on the basis of spectroscopic studies.

Coumarins↗

Evaluation of vancomycin use in a pediatric teaching hospital based on CDC criteria.

This study was performed to determine whether vancomycin use at our pediatric hospital was consistent with modified Centers for Disease Control and Prevention guidelines. Vancomycin use was inappropriate in 54% of patients. Inappropriate use briefly decreased by 14% after educational efforts. Further education regarding vancomycin use was deemed necessary and is continuing.

Centers for Disease Control and Prevention, U.S.↗

Papanicolaou smear sensitivity for adenocarcinoma in situ of the cervix. A study of 34 cases.

The sensitivity of cervical smears for adenocarcinoma in situ (AIS) is not known, nor is it known whether false-negative smears are due to sampling or to screening or interpretive errors. In 16 of 34 patients with AIS, 38 negative smears were reported 2 weeks to 7 years before biopsy. Thirty-one of these negative smears were rescreened, and 17 (55%) were retrospectively diagnosed as abnormal. Ten of the 17 had numerous well-preserved AIS cells: 5 with very small, crowded AIS cells, possibly originally mistaken for endometrial cells, and 5 with large groups in which AIS cells resembled reactive endocervical cells. Four smears were confirmed sampling errors. The sensitivity of cervical smears for AIS was 55% to 72%. Improved sampling of the endocervical canal offers cytologists the opportunity to diagnose AIS. This study demonstrates that this opportunity may not be fully exploited. Small "endometrioid" AIS cells and AIS cells resembling reactive endocervical cells may be mistaken for benign cells, thus decreasing sensitivity.

Adenocarcinoma↗

Total hip arthroplasty with an uncemented femoral component. Excellent results at ten-year follow-up.

We followed 138 patients (145 hips) who had had uncemented total hip arthroplasty using the Taperloc femoral component for a mean of ten years (8 to 12.5). No patient was lost to follow-up; 31 (31 hips) died before the minimum time of eight years for inclusion in the study, and 30 of these still had their femoral component in place. One well-fixed prosthesis had been exchanged at the time of acetabular revision. Of the remaining 114 hips, one femoral component required revision for aseptic loosening and one for sepsis. Three other well-fixed femoral components were removed during acetabular revision. Complete clinical and radiological follow-up was obtained in the 109 hips which had not had revision. Clinically, 94 (87%) were rated good or excellent, eight (7%) fair and seven (6%) poor. The average Harris hip score increased from 48 before operation to 88 at the time of the last follow-up. Radiologically, 103 hips (94%) had fixation by bone ingrowth, three (3%) showed stable fibrous ingrowth and three (3%) were unstable. Osteolysis of the fomoral cortex was seen in seven hips (6%), with major lysis in only one. At a mean follow-up of ten years, the results of the Taperloc femoral component are comparable with those of modern techniques of cementing in primary total hip arthroplasty.

Acetabulum↗

Mechanisms of edema formation after intracerebral hemorrhage: effects of thrombin on cerebral blood flow, blood-brain barrier permeability, and cell survival in a rat model.

Recently, the authors showed that thrombin contributes to the formation of brain edema following intracerebral hemorrhage. The current study examines whether the action of thrombin is due to an effect on cerebral blood flow (CBF), vasoreactivity, blood-brain barrier (BBB) function, or cell viability. In vivo solutions of thrombin were infused stereotactically into the right basal ganglia of rats. The animals were sacrificed 24 hours later; CBF and BBB permeability were measured. The actions of thrombin on vasoreactivity were examined in vitro by superfusing thrombin on cortical brain slices while monitoring microvessel diameter with videomicroscopy. In separate experiments C6 glioma cells were exposed to various concentrations of thrombin, and lactate dehydrogenase release, a marker of cell death, was measured. The results indicate that thrombin induces BBB disruption as well as death of parenchymal cells, whereas CBF and vasoreactivity are not altered. The authors conclude that cell toxicity and BBB disruption by thrombin are triggering mechanisms for the edema formation that follows intracerebral hemorrhage.

Animals↗

Seizures induced by intracerebral injection of thrombin: a model of intracerebral hemorrhage.

The coagulation cascade plays an important role in brain edema formation caused by intracerebral blood. In particular, thrombin produces brain injury via direct brain cell toxicity. Seizures and increased cerebral electrical activity are commonly associated with intracerebral blood and are possible effects of thrombin leading to cell injury in the brain. In this study, artificial clots containing concentrations of thrombin found in hematomas were infused intracerebrally in rats. The animals were observed clinically for seizure activity, behavior, and neurological deficits. Several animals underwent video electroencephalographic (EEG) monitoring during intracerebral infusion and for 30 minutes postinfusion. All animals were killed 24 hours after injection, and brain water and ion contents were measured to determine the amount of brain edema. Clinically, thrombin produced focal motor seizures in all animals. None of the control animals or those receiving N[alpha]-(2-Naphthalenesulfonyl-glycyl)-4-amidino-DL-phenylalanine -piperidide (alpha-NAPAP), a thrombin inhibitor added to the thrombin, showed clinical evidence of seizures. Of the rats undergoing EEG monitoring, all animals receiving thrombin showed electrical evidence of seizure activity, whereas none of the control animals exhibited seizure activity. There was no evidence of seizure activity on EEG monitoring when alpha-NAPAP was injected along with the thrombin. In addition, the artificial clots containing thrombin produced agitation and a circling tendency in the rats, along with brain edema. These results indicate that the coagulation cascade is involved in seizure production and increased brain electrical activity, which contribute to the neurological deficits and brain edema formation that are seen with intracerebral hemorrhage.

Animals↗

Wear of polyethylene acetabular components in total hip arthroplasty. An analysis of one hundred and twenty-eight components retrieved at autopsy or revision operations.

We evaluated the rates of volumetric wear and the patterns of wear of 128 acetabular components retrieved during an autopsy or a revision operation between one and twenty-one years after total hip arthroplasty. Twenty-two all-polyethylene components were retrieved at autopsy from hips that had been functioning well at the time of death (Group A). The remaining 106 components--eighty-four all-polyethylene components (Group B) and twenty-two metal-backed components (Group C)--were retrieved during revision operations. All 128 components had been inserted with cement. The mean rate of volumetric wear, determined directly with a fluid-displacement method, was thirty-five cubic millimeters per year (range, eight to 116 cubic millimeters per year) for Group A, sixty-two cubic millimeters per year (range, eight to 256 cubic millimeters per year) for Group B, and ninety-four cubic millimeters per year (range, twelve to 284 cubic millimeters per year) for Group C. Multivariate regression analysis showed a significant relationship (p < 0.05) between the size of the femoral head and the calculated mean annual rate of volumetric wear. The rate of volumetric wear was highest in association with thirty-two-millimeter femoral heads and lowest in association with twenty-two-millimeter heads; according to linear regression analysis, this represented a 7.5 per cent increase (Group A) or a 10 per cent increase (Group B) in the rate of wear for every one-millimeter increase in the size of the head. Linear regression analysis also showed a significant relationship between the duration that the implant had been in situ and the rate of wear (p < 0.05), with the rate being highest initially after the operation and decreasing with an increasing duration in situ. With the numbers available, the patient's age and gender and the side of the arthroplasty did not have a significant relationship to the annual rate of volumetric wear. Increased thickness of the polyethylene was related to a decreased rate of wear (p < 0.05) in the group of metal-backed components, which had a 25 per cent increase in the rate of wear for every one-millimeter decrease in thickness, but not in the other groups. The estimated median annual rates of wear, after adjustment of confounding variables to a hypothetical constant set of median values for the parameters (duration in situ, 132 months; diameter of the femoral head, twenty-six millimeters; and thickness of the polyethylene, eight millimeters), were significantly different among the three groups of components (p < 0.05). Histological evaluation of the worn surfaces showed the predominant mechanisms of wear to be abrasion and adhesion rather than fatigue-cracking or delamination. The highly worn areas were polished to a glassy finish on gross examination, but scanning electron microscopy showed numerous multidirectional scratches along with fine, drawn-out fibrils with a diameter of one micrometer or less oriented parallel to each other. These fibrils are the most likely source of submicrometer wear particles. Thus, wear appeared to occur mostly at the surface of the components and to be due to large-strain plastic deformation and orientation of the surface layers into fibrils that subsequently ruptured during multidirectional motion.

Acetabulum↗

The role of the coagulation cascade in brain edema formation after intracerebral hemorrhage.

The coagulation cascade has a potential role in brain edema formation due to intracerebral hemorrhage. In this study blood and other solutions were injected stereotactically into the right basal ganglia in rats. Twenty-four hours following injection, brain water and ion contents were measured to determine the amount of brain edema. Intracerebral blood resulted in an increase in brain water content. The amount of brain edema surrounding the intracerebral hematoma was reduced by a thrombin inhibitor N alpha-(2-Naphthalenesulfonylglycyl)-4-amidino-DL-phenylalaninep iperidide, (alpha-NAPAP) infused into the hematoma after the clot had been allowed to solidify. The inhibitor did not alter the actual size of the clot mass. An artificial clot composed of fibrinogen, thrombin, and styrene microspheres also produced brain edema. A fibrin clot led to edema formation even in the absence of mass effect provided by the microspheres. The single component responsible for production of brain edema in all these models was thrombin. The edema was formed in response to a fibrinogen-independent pathway. These results indicate that the coagulation cascade is involved in brain edema that develops adjacent to an intracerebral hematoma.

Animals↗

Cytologic findings in minimal deviation adenocarcinoma (adenoma malignum) of the cervix. A report of seven cases.

Minimal deviation adenocarcinoma (MDA) is a rare extremely well-differentiated form of invasive cervical adenocarcinoma. Because of its rarity and perhaps because cytologic changes are subtle and may be missed, there are only a few reports that illustrate the cytologic features of this neoplasm. To better understand the presentation of MDA in cervical smears and the role of cytology in diagnosing this lesion, the authors reviewed the clinical, histologic, and cytologic finding in seven patients. In two cases, MDA was an incidental finding in the a hysterectomy specimen. Three patients had a vaginal discharge and one patient had a "beefy red" cervix noted on pelvic examination. Although all 7 patients had cervical smears taken within 1 to 17 months before biopsy, in only one of the patients did the cervical smear lead to the diagnosis. On review, all smears from four patients were considered normal. In six smears from the remaining three patients, there were abnormal glandular cells that ranged from atypical to suspicious for well-differentiated adenocarcinoma in retrospect. All of these patients had minor foci of less well-differentiated carcinoma in their tumors. In 11 smears from 5 patients, including the smears with diagnostic cells, there were cells that we believe were from the MDA, but may not be diagnosable as malignant even in retrospect. These cells have not been described before in association with MDA. They are enlarged glandular cells, usually in honeycombed sheets with abundant cytoplasm. Nuclei are uniform with fine chromatin and small nucleoli. They lack pleomorphism and mitoses are only occasionally seen. We believe that in the absence of focal areas of more poorly differentiated adenocarcinoma, these cells are not sufficiently distinct from reactive endocervical cells to allow for a definitive diagnosis. However, awareness of their appearance, especially if seen in large sheets may allow the smear to be diagnosed as abnormal and lead to the correct diagnosis on a biopsy.

Adenocarcinoma, Mucinous↗