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Differential values of Ki-67 index and mitotic index of proliferating cell population. An assessment of cell cycle and prognosis in radiation therapy for cervical cancer.

BACKGROUND: Little is known about correlations between the growth fraction determined immunohistochemically with Ki-67 antibody and radiation response or prognosis after radiation therapy. METHODS: The prognostic value of the growth fraction determined by Ki-67 index and the mitotic index of proliferating cell population (pMI) were assessed in 45 cervical cancers treated with radiation therapy. The specimens from the cervix before radiation therapy were immunohistochemically stained with anti-Ki-67 antibody. RESULTS: The mean Ki-67 index and pMI for all patients were 36.0% and 2.74%, respectively. The patients with a Ki-67 index of 33% or greater showed significantly better histologic response to radiation at 30 Gy than those with less than 33%. The mean Ki-67 index for patients with good prognosis was significantly higher than for patients with tumor recurrence or metastasis later. Further, the mean values of pMI for patients with good prognosis were significantly lower than for patients with recurrence or metastasis. The 3-year survival rate for higher Ki-67 index (> or = 33%) was significantly better than lower Ki-67 index (less than 33%) (90.9% versus 34.8%; P < 0.001). However, the 3-year survival rate for higher pMI (> or = 3.5%) was significantly poorer than lower pMI (less than 3.5%) (8.3% versus 81.8%; P < 0.001). CONCLUSIONS: These results suggested that tumors with a high growth fraction showed a good prognosis with radiation therapy. In addition, the inverse prognostic correlation between the Ki-67 index and pMI suggested that both indices have independent values on radiation response and prognosis after radiation therapy.

Biomarkers, Tumor↗

The functional relationship between in vivo bromodeoxyuridine labeling index and Ki-67 proliferation index in human breast cancer.

Proliferation indices are used, along with other parameters, to estimate the risk of recurrence of breast cancer for individual patients. Because it is unlikely one index will be practical for all patients, it is important to understand the relationship between various indices of proliferation. For this reason, we compared a proliferation index based on in vivo labeling of S-phase tumor cells with the thymidine analog bromodeoxyuridine (BrdUrd), to a proliferation index based on an estimate of the growth fraction with the MIB-1 antibody to the Ki-67 antigen. With informed consent, we gave 145 patients 200 mg/m2 BrdUrd intravenously just prior to surgical removal of breast cancer. On histology sections, we visually counted S-phase cells which had incorporated BrdUrd using the Br-3 antibody which is specific to DNA-incorporated BrdUrd, and we counted cells in the growth fraction using the MIB-1 antibody to the Ki-67 antigen. We found that both indices were positively correlated with tumor size, number of positive nodes, and tumor grade, and both were negatively correlated with age and estrogen-progesterone receptor positivity. Using a linear functional relationship model, we found that the best (i.e. the maximal) fit between the two indices (correlation coefficient 0.79; p < 0.0001) occurred when each index was square root transformed, as is appropriate when counts follow a Poisson distribution. When we used the median as a cutpoint for each index, the classification of 19 percent of data pairs changed depending upon which index was used. We also estimated that the Ki-67 intercept (1.02 +/- 0.25) was significantly greater than zero. We conclude that the BrdUrd index of DNA synthesis in S-phase correlates highly with the MIB-1 index of the growth fraction, and both indices correlate well with other parameters of tumor aggressiveness. Because this correlation is driven by concordance of the extremes of high and low counts, clinical comparison will be necessary to determine which is the better prognostic marker for human breast cancer.

Adult↗

Volume corrected mitotic index (M/V index) in human bladder cancer; relation to histological grade (WHO), clinical stage (UICC) and prognosis.

A retrospective study was performed on 83 bladder cancer patients diagnosed at the Department of Surgery, Kuopio University Central Hospital, during the years 1965-1987. The follow-up time was 22 years, and the mean follow-up time of individual patients was 13 years (range 9.4-22 years). Histological grade (WHO), volume corrected mitotic index (M/V index) and clinical stage (UICC) were correlated to the survival of patients. Histological grade, M/V index and clinical stage were associated with crude survival (all causes of death included) with little predictive power. The recurrence of the disease could be predicted by the M/V index, but not by histological grade or clinical stage. When bladder cancer deaths only were included, histological grade (chi 2 = 26.6, p less than 0.001), M/V index (chi 2 = 6.6, p = 0.042) and clinical stage (chi 2 = 31.7, p less than 0.001) were clearly associated with prognosis. Also the metastasizing potential of bladder carcinomas could be predicted by the M/V index and by the histological grade at the time of primary diagnosis. Histological grade and M/V index were positively correlated (chi 2 = 16.7, p = 0.002, r = 0.47). In multivariate analysis clinical stage, histological grade and M/V index predicted prognosis in the order of importance.

Aged↗

What the Index Medicus indexes, and why.

The main criterion for selecting journals for indexing in Index Medicus, and thereby largely in MEDLARS, is quality. Subject scope varies with the voiced needs of the biomedical community. The Index aims to cover the best journals in all relevant subject fields, but the percentage of journals on a subject indexed depends on the quality of each journal. Country and language coverage depends on quality, even in the case of the best journals of each, although American biases may affect such selection. While a number of guidelines exist for identifying quality journals, information necessary to apply them confidently is often difficult to obtain. The National Library of Medicine is advised by an Ad Hoc Panel on the Selection of Journals for Index Medicus, composed both of NLM officers and extramural members. Criticism has been voiced that too many titles are indexed, compared with titles actually used, but no meaningful statistics of use exist which can identify titles which should be excluded from indexing. Continuing suggestions from users regarding titles indexed would benefit everyone.

Abstracting and Indexing↗

Prognostic significance of tumor markers in colorectal cancer patients: DNA index, S-phase fraction, p53 expression, and Ki-67 index.

Risk of colorectal cancer recurrence has traditionally been determined by use of pathologic staging. However, it is apparent that subgroups of patients exist within tumor stages whose clinical behavior differs. This study was undertaken to identify tumor-associated factors that might be predictive of outcome in patients with intermediate stages who will benefit the most from postsurgical adjuvant therapy. Seventy patients with stage II and III colorectal cancer were assessed for DNA index, S-phase fraction, p53 expression, and Ki-67 index. Tumor recurrence was analyzed by means of nonparametric tests and Cox proportional hazard models incorporating standard clinical and pathologic criteria. Of the four prognostic markers evaluated, Ki-67 index was significantly associated with disease recurrence (P = 0.02), whereas DNA index, S-phase fraction, and p53 expression were not. After stratification by tumor stage, significant associations between Ki-67 index and disease recurrence were retained in stage II tumors (P = 0.01) but not in stage III tumors (P = 0.23). Cox proportional hazard regression analysis indicated that among stage II patients, those with a Ki-67 index >45% were associated with 6.5 times greater risk for disease recurrence than those with a Ki-67 index >/=45%. It was concluded that an elevated Ki- 67 index is associated with an increased risk of tumor recurrence in stage II colorectal cancer.

Aged↗

The effects of ketamine and rocuronium on the A-Line auditory evoked potential index, Bispectral Index, and spectral entropy monitor during steady state propofol and remifentanil anesthesia.

BACKGROUND: The authors studied the effects of ketamine and rocuronium on the Bispectral Index, A-Line auditory evoked potential index, state entropy, and response entropy during a calculated steady state anesthesia with propofol and remifentanil. METHODS: After ethics committee approval, 42 patients were allocated to four groups. Baseline measurements were performed after implementing a calculated steady state anesthesia with propofol and remifentanil. The control group received no additional medication. The ketamine group received a bolus and continuous infusion of ketamine. The rocuronium group received a bolus of rocuronium. The rocuronium-ketamine group received both. All data were stored during 15 min after baseline. After inspection of the raw data, the authors conducted an explorative statistical analysis. RESULTS: No significant changes were found in the control group for any of the monitors. Mean values decreased in the rocuronium group for the A-Line auditory evoked potential index, Bispectral Index, and response entropy, but not for state entropy. In the ketamine group, the A-Line auditory evoked potential index and Bispectral Index did not change significantly, but state and response entropy increased. In the rocuronium-ketamine group, the A-Line auditory evoked potential index and Bispectral Index did not decrease as found in the rocuronium group. Response and state entropy increased significantly. CONCLUSIONS: The response of all monitors after ketamine administration is not affected by simultaneous administration of rocuronium. Interpretation of all studied indices must be done cautiously while taking into account the clinical setting during measurement.

Adolescent↗

Functional assessment by myocardial performance index (Tei index) correlates with plasma brain natriuretic peptide concentration in patients with hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) might exhibit not only diastolic, but also latent systolic dysfunction. Therefore combined assessment of both systolic and diastolic function using myocardial performance index (Tei index) can be useful in HCM. Plasma brain natriuretic peptide (BNP) level is reported to be elevated in HCM, but the mechanism of BNP elevation in HCM remains to be established. METHODS AND RESULTS: The value of Tei index in 45 HCM patients was compared with that of 20 normal control subjects. The HCM patients showed a higher value of Tei index (0.55+/-0.12 vs 0.36+/-0.08, p < 0.0001) and longer isovolumic relaxation and contraction times than control subjects. The plasma BNP level correlated with Tei index in non-obstructive HCM (n = 35, r = 0.61, p < 0.0001), although the correlation was mild when overall HCM patients were included (r = 0.34, p = 0.02). The correlation was still significant after adjusting for age, or the extent and severity of left ventricular hypertrophy. Multiple stepwise regression analysis identified mitral E/A ratio (r = 0.49, F = 13.1) and Tei index (r = 0.37, F = 7.6) as independent predictors of higher plasma BNP level in non-obstructive HCM. CONCLUSIONS: Myocardial performance index was abnormal in HCM, reflecting both systolic and diastolic dysfunction in this disorder. Plasma BNP level correlated with functional assessment by Tei index in non-obstructive HCM.

Adult↗

An evaluation of the Kessner Adequacy of Prenatal Care Index and a proposed Adequacy of Prenatal Care Utilization Index.

OBJECTIVES: The assessment of the adequacy of prenatal care utilization is heavily shaped by the way in which utilization is measured. Although it is widely used, the current major index of utilization, the Kessner/Institute of Medicine Index, has not been subjected to systematic examination. This paper provides such an examination. METHODS: Data from the 1980 National Natality Survey are used to disaggregate the components of the Kessner Index for detailed analysis. An alternative two-part index, the Adequacy of Prenatal Care Utilization Index, is proposed that combines independent assessments of the timing of prenatal care initiation and the frequency of visits received after initiation. RESULTS: The Kessner Index is seriously flawed. It is heavily weighted toward timing of prenatal care initiation does not distinguish timing of initiation from poor subsequent utilization, inaccurately measures utilization for full- or post-term pregnancies, and lacks sufficient documentation for consistent computer programming. CONCLUSIONS: The Adequacy of Prenatal Care Utilization Index offers a more accurate and comprehensive set of measures of prenatal care utilization than the Kessner Index.

Algorithms↗

Relationships between a proprietary index, bispectral index, and hemodynamic variables as a means for evaluating depth of anesthesia in dogs anesthetized with sevoflurane.

OBJECTIVE: To evaluate relationships among various techniques for monitoring anesthetic depth in sevoflurane-anesthetized dogs undergoing orthopedic surgery. ANIMALS: 10 dogs. PROCEDURE: Dogs were medicated with acepromazine (0.05 mg/kg, IM), buprenorphine (0.01 mg/kg, IM), and atropine (0.04 mg/kg, IM). Anesthesia was induced and maintained with sevoflurane. Cardiovascular and respiratory responses were monitored. Anesthetic depth was monitored by use of the bispectral index (BIS), and a proprietary index was used to monitor activity of the autonomic nervous system. RESULTS: A significant decrease in BIS was seen after induction but concurrent changes were not observed for the other techniques. The proprietary index increased significantly after intubation, but no changes were seen for the other techniques. No significant changes were detected during incision or when higher nociceptive stimuli were applied. We did not identify a correlation between BIS and the proprietary index, the proprietary index and hemodynamic variables, or the BIS and hemodynamic variables during induction and maintenance. A significant increase in the proprietary index and BIS was detected at the time of resumption of reflexes. During anesthetic recovery, a correlation was found between the proprietary index and BIS but not between hemodynamic variables and the other techniques. CONCLUSIONS AND CLINICAL RELEVANCE: A significant increase in the proprietary index, but not the BIS or hemodynamic variables, was detected during intubation. Anesthetic induction with sevoflurane did not prevent the sympathetic stimulus attributable to tracheal intubation. Monitoring of hemodynamic variables does not provide sufficient information to allow clinicians to evaluate stress during anesthetic recovery.

Acepromazine↗

[Evaluation of restenosis after percutaneous transluminal coronary angioplasty using a Doppler index, the Tei index].

Cardiac function and restenosis were evaluated after percutaneous transluminal coronary angioplasty (PTCA) using a Doppler index (the Tei index). Thirty-eight patients, 31 men and 7 women (mean age 57 years) with ischemic heart disease were studied. The underlying heart diseases were angina pectoris without left ventricular asynergy in 16 patients and old myocardial infarction (OMI) with left ventricular asynergy in 22 . Ejection fraction was measured by M-mode echocardiography and deceleration time, and the interval between cessation and onset of the mitral inflow velocity (a), ejection time at aortic valve (b), and the Tei index [(a-b)/b] were measured by M-mode echocardiography performed before and 6 months after PTCA. The ejection fraction, deceleration time and Tei index showed no changes after PTCA in patients with angina pectoris with or without restenosis. In patients with OMI with restenosis, the Tei index increased slightly after PTCA, from 0.56 +/- 0.15 to 0.61 +/- 0.13. The deceleration time changed from 0.23 +/- 0.03 to 0.24 +/- 0.02 msec, and the ejection fraction from 0.46 +/- 0.11 to 0.51 +/- 0.17, neither significantly. However, in patients with OMI without restenosis (15 out of 22 patients), the Tei index significantly improved after PTCA, from 0.55 +/- 0.13 to 0.48 +/- 0.12 (p < 0.05). In patients with left ventricular asynergy due to old myocardial infarction, without restenosis, the Tei index significantly improved after PTCA. The Tei index is useful for evaluating restenosis after PTCA in patients with OMI.

Angina Pectoris↗

A comparison of drug literature coverage by Index Medicus and Drug Literature Index.

We compared Index Medicus and Drug Literature Index during a search concerning the toxicity of eight drugs used in treating tropical diseases. Indexes covering the years 1969, 1970, and 1971 were searched. Index Medicus produced 198 citations and Drug Literature Index 309. There were seventy citations that appeared in both indexes, a duplication of 16%. Highest percentage of duplication for any one drug was 38.9%. We concluded that Index Medicus and Drug Literature Index provide complementary coverage in the area of drug toxicity and that, therefore, both tools should be consulted in searches of this nature.

Bibliographies as Topic↗

Individual risk factors for carpal tunnel syndrome: an evaluation of body mass index, wrist index and hand anthropometric measurements.

In this study we aimed to identify the role of the body mass index (BMI), wrist index and hand anthropometric measures as risk factors for carpal tunnel syndrome (CTS) in both genders. Based on clinical and electrophysiologic diagnostic criteria, 154 female and 44 male CTS patients, as well as 150 female and 44 male age-matched control subjects, were selected. BMI, wrist index, hand shape index, digit index and hand length/height ratio were compared between the CTS patients and the control subjects for each gender separately. Mean BMI was found to be a significant risk factor for CTS in both genders. The wrist index was found to be higher in female (P < 0.001) and in male (P = 0.034) CTS groups than in the respective control groups. Logistic regression analysis revealed the wrist index to be an independent risk factor in females, but not in males. Shape and digit indices were significantly higher in female CTS patients than in corresponding control subjects, and regression analysis showed the shape and digit indices to be independent risk factors for CTS. In the male CTS group, the shape and digit indices did not significantly differ from their controls. Differences in the hand length/height ratio were not statistically significant in female and male CTS patients compared to their controls and it was not found to be an independent risk factor for CTS. Our study confirmed BMI as an independent risk factor for CTS in both genders. Hand and wrist anthropometrics were found to be independent risk factors for CTS in females, but not in males.

Action Potentials↗

Performance of the thrombolysis in myocardial infarction risk index in the National Registry of Myocardial Infarction-3 and -4: a simple index that predicts mortality in ST-segment elevation myocardial infarction.

OBJECTIVES: We sought to evaluate a simple risk index based on age and vital signs in a community sample of patients with ST-segment elevation myocardial infarction (STEMI). BACKGROUND: A simple risk index based on age and vital signs (heart rate x [age/10](2)/systolic blood pressure) developed from patients with STEMI accurately predicts mortality in clinical trials of fibrinolysis. The application of such a tool in an unselected population is necessary to evaluate its utility in clinical practice. METHODS: To evaluate the Thrombolysis In Myocardial Infarction (TIMI) risk index for routine practice, we tested it in the National Registry of Myocardial Infarction (NRMI)-3 and -4. The risk index was evaluated as a continuous variable in patients with STEMI from NRMI and in subgroups based on age and reperfusion status. RESULTS: A total of 153,486 patients with STEMI were eligible. As anticipated, STEMI patients in NRMI had a higher risk index profile, as compared with those in the clinical trial (median 26.9 vs. 20, p < 0.0001). Classification of NRMI patients with STEMI into risk groups revealed a significant graded relationship with mortality (0.9% to53.2%, p(trend) < 0.0001, c statistic 0.79). The discriminatory capacity of the risk index was particularly strong in the 81,679 patients receiving reperfusion therapy (0.6% to60%, p(trend) < 0.0001, c statistic 0.81). For the 71,807 patients not receiving reperfusion therapy, a strong graded relationship remained (1.9% to 52.2%, p(trend) < 0.0001, c statistic 0.71). Among the elderly, although the distribution of scores was shifted toward higher risk, the performance remained (0% to 53.1%, p(trend)< 0.0001, c statistic 0.71). CONCLUSIONS: A simple risk index from baseline clinical variables routinely obtained at the first patient encounter predicted mortality in a large unselected heterogeneous group of patients with STEMI.

Aged↗

Gender-related differences in scores of the Barthel Index and Frenchay activities index in randomly sampled elderly persons living at home in Japan.

The purpose of this study was to examine for gender-related differences in activities of daily living (ADL) and lifestyle of elderly persons living at home, and to support our hypothesis that the gender-related difference in lifestyle of stroke patients derives from their lifestyle prior to the stroke. Participants were randomly sampled elderly persons living at home. Questionnaire sheets including subject profile, Self-Rating Barthel Index (disability index), and Self-Rating Frenchay Activities Index (activity index) were mailed and collected, and the data were analyzed with the t-test and General Linear Model (factorial model with interaction). A total of 752 subjects were recruited, and their average age was 67.1 years. No significant gender-related differences were evident in the disability index including self-care and mobility domains (t-test, P > 0.05). In contrast gender-related differences in the activity index were significant (t-test, P < 0.05) for three factors; gender, age group, and living conditions, and in a covariate disability index (GLM, P < 0.05). Because randomly selected elderly persons in this study exhibited a prominent gender-related difference in lifestyle, we believe the lifestyle difference in stroke patients that we have previously described derives primarily from their premorbid attitude to daily life.

Activities of Daily Living↗

ADM-INDEX: an automated system for indexing and retrieval of medical texts.

ADM-INDEX is a system for indexing and retrieval of Patients Discharge Summaries (PDSs) by using linguistic methods (morphologic, syntaxic and semantic processing). The ADM-INDEX knowledge base is a restructuring of a diagnostic aid knowledge base (ADM) in order to allow the linguistic analysis of medical texts. The ADM system is a comprehensive medical knowledge base which has been developed since 1972 at the University Hospital of Rennes and which has been the first professional videotex medical diagnostic aid in France. After linguistic analysis, ADM-INDEX build the index table with thesaurus wording, medical words, concepts and phrases, unknown words contained in each PDS. The benefit of using those different elements is to improve information retrieval. Although our system is constructed with the ADM dictionary, it can be easily applied to other medical nomenclature or thesaurus. In this paper, we present on the one hand the ADM-INDEX knowledge base which is constituted by rules, a dictionary and a thesaurus, and on the other hand, the process of indexing and retrieval information.

Abstracting and Indexing↗

The NLM Indexing Initiative's Medical Text Indexer.

The Medical Text Indexer (MTI) is a program for producing MeSH indexing recommendations. It is the major product of NLM's Indexing Initiative and has been used in both semi-automated and fully automated indexing environments at the Library since mid 2002. We report here on an experiment conducted with MEDLINE indexers to evaluate MTI's performance and to generate ideas for its improvement as a tool for user-assisted indexing. We also discuss some filtering techniques developed to improve MTI's accuracy for use primarily in automatically producing the indexing for several abstracts collections.

Abstracting and Indexing↗

Development and validation of an index for scoring baseline respiratory disease in the very low birth weight neonate. Severity Index Development and Validation Panels and Newborn Lung Project.

An accurate description of the population at risk for neonatal chronic lung disease is clearly of prime importance for comparative studies and the planning of interventions. Attempts to explain variations in chronic lung disease rates in such studies have been compromised by lack of a way of estimating the severity of the initial pulmonary disease as a risk factor. Therefore, a severity index was developed for use in very low birth weight (less than 1501 g) neonates. Special emphasis was placed on applicability of the index in the multicenter observational setting. Development followed a clinician panel approach, with the resulting index designed to capture clinical judgment of severity. The index was validated prospectively on neonates in a neonatal intensive care unit, and retrospectively using charts from nine hospitals nationwide. Correlations of the index with clinical judgment in the two samples were .95 and .93, respectively. In an additional validation the index combined with birth weight correctly predicted oxygen dependence status at 30 days in 36 of 42 neonates consecutively admitted to five neonatal intensive care units (P = .002). Birth weight and the severity index contributed about equally to the prediction, and therefore they seem to represent partly independent components of baseline propensity for prolonged oxygen dependence.

Apgar Score↗

Prognostic significance of the immunohistochemical index of survivin in glioma: a comparative study with the MIB-1 index.

OBJECTIVE: Survivin has been identified as a protein expressed in cancer cells and a member of the inhibitor-of-apoptosis protein family. Recent studies suggest that the expression of survivin increases during the G2/M phase of the cell cycle, and may be used in clinical prognosis. We examined whether survivin expression in human gliomas would be a correlative of prognosis. METHODS: We prepared polyclonal anti-survivin serum to establish a survivin index for stained sections, using an immunohistochemical procedure, according to the method used for scoring MIB-1 index, and then stained 29 paraffin-embedded sections from surgical specimens of 29 patients who were classified into three grades of World Health Organization with the mean age of low grade astocytoma (grade II) being 34.7; anaplastic astrocytoma (grade III), 48.8; and glioblastoma multiform (grade IV), 58.4. RESULTS: On staining with the anti-survivin antiserum, all specimens contained positive cells, but the survivin index was heterogeneous among grades. The mean percentage of immunoreactive cells in each specimen was 70.0 (SD 18.2) in grade II, 81.3 (16.5) in grade III, and 85.0 (13.6) in grade IV. Then we compared the survivin index to the MIB-1 index and found that in low-grade gliomas (grade II and III), the difference in survival times between the high and low survivin indexes was significant (P=0.007), whereas that between the high and low MIB-1 indexes was not significant (P=0.092). ONCLUSION: Survivin is more sensitive marker than MIB-1 for the evaluation of low-grade gliomas in that it helps to predict patient survival. Much larger glioma patient series are needed to validate the findings of our limited study.

Adult↗