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[Biological dose assessment by the analyses of chromosomal aberrations and CB micronuclei in two victims accidentally exposed to 60Co gamma-rays].

Biological doses were estimated by using the yields of dicentrics plus rings(dic+r) and cytokinesis-block micronuclei (CBMN) for two victims of the accident radiation occurred on Mar 6,2000 in the City of Xuchang(victim A), and Jun 26,2000 in the City of Kaifeng(victim B), Henan Province,respectively. The results indicated that the equvalent whole body doses based on the standard dose-response curves established by the analyses of dic+r and CBMN were estimated to be 1.44Gy and 1.43Gy(victim A), and 0.15Gy and 0.22Gy(victim B). These doses were very consistent with the mean doses calculated from physical measurement and conformable to the clinical dianosis. The dic+r aberrations of victim A did not accord with Poisson distribution. The analyses of chromosomal aberrations and CBMN are an extremely reliable method in biological dosimetry. The radiation which victim A was exposed to was heterogeneous.

English Abstract↗

Mortality in a complete 4-year follow up of 85-year-old residents of Leiden, classified by serum level of thyrotropin and thyroxine.

BACKGROUND: The authors of the source article emphasize the clinical tendency to screen for, detect and treat for thyroid dysfunction in very elderly patients, in which it is a fairly common disorder, often with occult or no symptoms. Published evidence is conflicting on the benefit, if any, of such a program. Accordingly, they devised a prospective, population-based study to determine outcomes, including survival outcome, based on serum levels of thyroid-stimulating hormone (TSH) and thyroxine. METHODS: A cohort of 558 subjects who had their 85th birthday between September 1997 and September 1999 was enrolled after consent of the subject and screening examination that included serum TSH and thyroxine levels. This represented a 79% sample of all 85-year-old residents of Leiden, the Netherlands. Follow up was complete for survival 4 years to the subject's 89th birthday or prior death, although 70 subjects refused the annual re-examination. Thyroid function, disability, cognitive function and number of chronic diseases were analyzed, in addition to mortality, through Cox regression and other statistical methods. RESULTS: In 67 subjects with abnormally high TSH (>4.8 mIU/ L), the mean annual mortality rate was derived as 64 deaths per 1000 per year. In the 491 subjects with normal TSH or low TSH (<0.3 mIU/L), the mean annual mortality rate was derived at 114 per 1000 per year. Laboratory evidence of hypothyroidism (initially low serum thyroxine) was found in only 37 of the 67 subjects. CONCLUSION: In the 13% of elderly subjects in Leiden with abnormally high serum TSH levels, the mean annual mortality rate was significantly lower than the mortality rate in the 87% of the elderly patients with normal or low serum TSH. The significance is based on 95% confidence levels of the Poisson distribution. The rate in the group with high TSH levels had 16 deaths in 264 person-years of follow up (FU). The majority with normal or low TSH levels had 193 deaths in 1698 person-years of FU.

Actuarial Analysis↗

Modelling predictions of cancer deaths in Northern Ireland.

BACKGROUND: An ageing population has service planners concerned about future levels of disease which are age dependent. Predictions of mortality for colorectal, lung and breast cancers, which account for 30% of cancer cases and 40% of cancers deaths, were calculated for 2010 and 2015, based on trends in death rates and the predicted change in the demography of the Northern Ireland population. METHODS: The U.S. National Cancer Institute's "Joinpoint" program was used to check for structural breaks in the time series of cancer death rates from 1984 to 2004. The prediction models applied to the data allowed variations in trends across age groups to be taken into account. A linear model was used for increasing or constant trends and a log linear model was used where the trend was decreasing. The models assume the number of deaths in each stratum, defined by age-sex and time-period, is Poisson distributed, with the average value determined by a log or linear function. RESULTS: Recent trends in rates of cancers studied were downwards except for female lung. Predictions include decreased colorectal cancer deaths in females and lung cancer deaths in males. In females, lung cancer deaths are predicted to more than double by the year 2015 (473 deaths), based on the 1984 level. Colorectal death rates in males are predicted to drop, but the number of deaths will increase by more than 10%, due to demographic change. Numbers of breast cancer deaths are likely to rise slightly, despite falling age standardised death rates, due to an ageing population. CONCLUSIONS: This work has provided estimates of early future trends, useful to service planners, and highlights the need for tobacco control, to reduce numbers of lung cancer deaths in females. The recently announced control of environmental tobacco legislation is one welcome development which should reduce lung cancer mortality in Northern Ireland.

Adolescent↗

Improved detection of cell death in vivo with annexin V radiolabeled by site-specific methods.

UNLABELLED: Labeled annexin V is widely used to detect cell death in vitro and in vivo. Nearly all studies have been done with annexin V derivatized via amine-directed bifunctional agents; it was thought that these molecules retained full bioactivity compared with unmodified protein. We now show that this assumption is incorrect by measuring the affinity of annexin V for cells in vitro by quantitative calcium titration under conditions of low membrane occupancy. METHODS: Annexin V was modified with 4 different amine-directed agents: the N-hydroxysuccinimide esters of hydrazinonicotinic acid, mercaptoacetyltriglycine, and biotin; and with fluorescein isothiocyanate. RESULTS: In all cases, the membrane-binding affinity was decreased by derivatization, even at very low average stoichiometries. A statistical model based on the Poisson distribution accurately predicted the observed heterogeneity of derivatization as a function of average derivatization stoichiometry. This model also showed that multiply derivatized forms, which are the ones most likely to have compromised bioactivity, contributed disproportionately to the binding and imaging signals. The in vitro binding assay correctly predicted in vivo uptake in a mouse liver model of apoptosis for all proteins tested. The annexin V-128 protein, labeled at a single specific site at the N terminus, showed twice as much apoptosis-specific liver uptake as did all forms of annexin V derivatized randomly via amino groups. CONCLUSION: The membrane-binding activity of annexin V is much more sensitive to amine-directed chemical modification than previously realized. New annexin V molecules labeled by site-specific methods will greatly improve sensitivity for detecting cell death in vivo.

Animals↗

[Time trends, estimates and projects for breast cancer incidence and mortality in China].

OBJECTIVE: Using comprehensive available data on women breast cancer in China, to describe the mortality trends from late 1970s, estimate and project the profile in 2000 and 2005, and to aim to provide a reference for clinic, basic research and prevention and control strategy making for breast cancer in China. METHODS: Using Joinpoint model, the mortality trends were analyzed on the basis of routine surveillance data. Combining with the data from the second national mortality survey and several cancer registries, using the log-linear model (based on Poisson distribution), the breast cancer profile in 2000 and 2005 were estimated and projected. RESULTS: Although there was a slight decline in mortality between early 1970s and 1990s, the age-specific mortality rates among young and middle age women increased dramatically which followed a continuing increase trend on both rates and absolute numbers, in both urban and rural areas in recent 15 years. Compared with 2000, there are 470 thousands more new breast cancer cases and 130 thousands more deaths from breast cancer in 2005. CONCLUSION: Due to the double effects of both increasing risk factors and population growth and ageing, breast cancer will be one of the most extensively increasing cancers in Chinese women. The prevention and control of breast cancer will be of great emphasis for future cancer control strategy in China.

Adolescent↗

Use of the Mantel-Haenszel chi 2 overestimates precision in studies with sparse data.

Probability values or "test-based" confidence limits computed on the basis of the Mantel-Haenszel chi 2 statistic may be invalid if minimum cell-size requirements are not met. In 30 studies of occupational proportionate mortality published from 1985 through 1987, the Mantel-Haenszel chi 2 was used in potential violation of cell-size requirements in 21 studies. Sixteen (76%) studies included at least one value that, when compared with testing with the Poisson distribution, was erroneously reported as statistically significant at the 0.05 level. We conclude that by using the Mantel-Haenszel chi 2 with sparse data, some epidemiologists overestimate precision.

Bias↗

The safety and cost-effectiveness of low osmolar contrast media. Can economic analysis determine the real worth of a new technology?

OBJECTIVES: To estimate the reduction in mortality associated with a reduced adverse reaction rate following the substitution of older high osmolar radiocontrast media (HOCM) by the newer and more expensive low osmolar contrast media (LOCM), and to assess the cost-effectiveness of switching from HOCM to LOCM in patients with and without underlying risk factors for adverse reactions from radiocontrast agents. DATA SOURCES: Data from large prospective studies of adverse reactions to HOCM and LOCM were used to estimate the expected number of deaths and severe non-fatal reactions in a hypothetical population receiving one million intravenous radiocontrast injections with HOCM, and the expected reduction in the frequency of these outcomes after substitution by LOCM in high-risk and low-risk groups respectively. Life-years lost with each radiocontrast-related death were estimated from an audit of fatal adverse reaction reports submitted to the Adverse Drug Reactions Advisory Committee. The direct costs considered in the study were the increased costs of LOCM and the hospital costs of treating radiocontrast reactions which were estimated from an audit of cases admitted to public hospitals in Newcastle. STUDY SELECTION: The literature search included Medline (1966-1989) and bibliographies of original and review articles. We included only studies which were prospective, monitored patients in a formal way, described a mechanism for the recording of adverse events and were of sufficient size to have been capable of detecting severe reactions to radiocontrast agents. DATA EXTRACTION: Data were extracted independently by two investigators, unblinded, with disagreements resolved by consensus. DATA SYNTHESIS: Mortality data from individual reports were pooled and exact confidence intervals were calculated on the assumption of a Poisson distribution. In the case of comparative studies the relative risks of severe reactions in low-risk versus high-risk patients and with LOCM compared with HOCM were treated for homogeneity, and pooled odds ratios and 95% confidence intervals (CI) were calculated by combining the logarithms of the odds ratios weighted by their variances. RESULTS: The mortality after intravenous administration of HOCM was estimated from all studies to be 23.3 (95% CI, 2.4-33.1) per million injections. However, the mortality was 11.7 per million (95% CI, 2.4-34.1) in studies published since 1986. The mortality after the use of LOCM was estimated as 3.9 per million (95% CI, 0.1-21.7).(ABSTRACT TRUNCATED AT 400 WORDS)

Australia↗

Blind serosurvey of HIV antibodies in newborns in 92 Italian hospitals: a method for monitoring the infection rate in women at time of delivery.

In Italy, drug abusers are the major risk category for HIV infection, representing 67% of all the reported cases of AIDS. This can in part explain the higher incidence of the infection observed in Italian females (17.7%) in comparison with the data reported in Europe (11.5%) or in the U.S. (8.5%). Therefore, anti-HIV screening in newborns reflects the serologic pattern of the respective mothers and can provide a useful tool in evaluating the incidence of the infection in a relatively unselected population. Furthermore, the data collected can provide a good predictive parameter for the rate at which pediatric AIDS will develop. Blood samples were collected on filter paper for routine screenings from 39,102 consecutive newborns in 92 hospital nurseries, from eight different Italian regions, during the period June 1988-April 1989. Blood-saturated disks were screened for anti-HIV antibodies (HIV Ab) using an ELISA; positive results were confirmed using a Western blot. Among the 39,102 blood samples tested, 51 (0.00130, 95% confidence intervals, Poisson distribution of 0.00097-0.00171) were found to be positive for HIV Ab. The distribution pattern of the positive samples among the different regions correlates to the cumulative AIDS incidence rate, with a higher prevalence in urban and industrialized areas.

Blotting, Western↗

Hyperthermic purging in vitro of murine leukemia cells (MK-8057): surviving fractions of normal and leukemic stem cells and the long-term survival of mice injected with the post-hyperthermic leukemia cells.

Hyperthermic purging of leukemic cells has been applied in clinical trials, although an accurate evaluation system to compare the effect on leukemia cells with that on normal hemopoietic cells has not been established. We evaluated the heat-sensitivity of murine leukemia cells, MK-8057, and compared differences in heat-sensitivity between surviving fractions of leukemic stem cells (leukemic spleen colony-forming units, L-CFU-S) and normal hemopoietic stem cells (spleen colony-forming units, CFU-S). Using the spleen colony assay, the survival fraction of L-CFU-S was compared with that of CFU-S after various hyperthermic treatments. One of the most efficient conditions, that is, hyperthermia at 42 degrees C for 3 h, allowed only 0.17% of L-CFU-S to survive, whereas 26.5% of normal CFU-S survived. Hyperthermia at 44 degrees C for 45 min further reduced the L-CFU-S (0.13%); however, the relative ratio of L-CFU-S to CFU-S was less than that at 42 degrees C for 3 h, because there was a larger reduction at 44 degrees C in normal CFU-S (5.1%). Recipient mice injected with MK-8057 cells treated with hyperthermia survived longer in proportion to the decreasing number of surviving L-CFU-S injected. This extension of the survival of recipient mice given MK-8057 cells after hyperthermia was also proportional to the estimated survival fraction of L-CFU-S. The survival fraction of MK-8057 cells after hyperthermia that was independently calculated through the extended survival of the recipients showed a good correlation with the surviving fraction of L-CFU-S, seen as the leukemic spleen colonies, at a correlation coefficient of r = 0.985. The number of surviving mice receiving the post-hyperthermic MK-8057 cells and the number of L-CFU-S calculated to have been injected had a relationship based on a Poisson distribution. Thus, the calculated results imply that the hyperthermia proportionally targets L-CFU-S, which are the only cells responsible for killing the recipient mice.

Animals↗

Epidemic curve characteristics for the Reed-Frost model.

Some useful approximations are developed in this paper that describe large-scale epidemic phenomena for the deterministic and stochastic Reed-Frost model. These characteristics provide an a priori quantitative description of the epidemic curve for the deterministic case, such as a threshold requirement, the total size of the epidemic, and the degree of skewness in the epidemic curve. A Poisson distribution asymptotically describes the distribution of the total size of an epidemic when the relative removal rate is well below threshold for the Reed-Frost chain binomial model. These properties are established by an extension of the large-scale epidemic phenomena of the Kermack-McKendrick model.

Binomial Distribution↗

X-radiation actions on the neuromuscular transmission.

The effects of high doses of X-radiation (100 kilorads) on the neuromuscular transmission of isolated sciatic nerve-sartorius muscle preparations of the frog, as evaluated by bioelectrical characteristics, were explored. Intracellular microelectrode recordings after X-irradiation showed that the resting, excitation and action potentials of nerve fibers approaching the synaptic terminal region of the motor end-plate became lessened, and also presented a slower velocity of impulse propagation, earlier than that observed in muscle cells. After forty minutes following the irradiation period, the neuromuscular transmission became blocked, although muscle fibers still responded to direct electrical stimulation. Records taken at the motor end-plate region of muscle cells, demonstrated the presence of postsynaptic miniature end-plate potentials (m.e.p.p.'s), the sequence of which fits closely into a random Poisson distribution. X-irradiation elicited an increase of the rate of m.e.p.p.'s and induced membrane changes over fine terminal nerve branches, leading into a failure to initiate and propagate action potentials. Only as time progressed, this nerve bioelectrical impairment was accompanied by a similar one in muscle cells, associated to the inability to develop contractile tension. The increase of m.e.p.p.'s frequency due to depolarization by a high K+ concentration, of presynaptic nerve membranes of control and irradiated preparations, was reversed by a high Mg+--Ca2+--free media. However, a concentration of Mg2+, which normally reduced quantal release of acetylcholine (ACh), without altering presynaptic nerve membrane potentials, failed to modify the spontaneous basal frequency of m.e.p.p.'s, both in irradiated and control preparations. The findings of the present study suggest that the presynaptic ACh synthesis, storage, and availability for ACh liberation are not early affected by X-rays, i.e. at a time when transmission from nerve to muscle had already failed. On the contrary, the most precocius membrane changes following X-irradiation, seem related to the mechanisms underlying nerve resting, excitation, and action potentials. The smallest presynaptic nerve terminal fibers close to the motor end-plate, are the most radiosensitive portion of the myoneural junction. Indeed, their bioelectric characteristics are early affected by X-rays, resulting in a failure to generate and propagate nerve impulses which lead to a blockade of neuromuscular transmission.

Action Potentials↗

[Automatic identification of structural gene fragments using a set of peptides].

A computer program is designed to facilitate the identification of coding gene's fragments using a set of peptides. The program is written on Basic programming language for personal computer "Iskra-226" (USSR). To accelerate some operations, computer code commands are used. Treatment of 50 DNA fragments by means of 10 peptides takes ca. 1 h of computer time. The program outputs list coding gene's fragments and corresponding peptides. The suggested algorithm is based on our finding that the number of false identifications of a coding gene fragments may be predicted by Poisson distribution and minimized using correct criteria. The suggested method enables one to evaluate the reliability of the true identification of DNA fragments in case of mistakes in primary structure of the gene fragments or peptides.

3',5'-Cyclic-GMP Phosphodiesterases↗

Mortality and cancer incidence in a cohort of commercial airline pilots.

We undertook a cohort study of all male pilots employed since January 1, 1950, by CP Air, now Canadian Airlines International. A total of 913 eligible pilots--630 active and 283 no longer employed--contributing 18,060 person-years of observation, were identified through company records. As of October 31, 1988, current status was obtained on 891 (97.6%). Standardized mortality ratio (SMR) and standardized incidence ratio (SIR) were used to compare, respectively, the mortality and cancer incidence of the cohort with that of the British Columbia population. Statistical significance of the SMR and SIR by comparison with the Poisson distribution (p less than 0.05 one-sided) and 90% confidence intervals (CI) were calculated. Excess deaths were observed for aircraft accidents (No. = 23; SMR = 21.29; p less than 0.001; CI 14.60, 30.20), brain cancer (No. = 4; SMR = 4.17, p = 0.017; CI 1.40, 9.50) and rectal cancer (No. = 3; SMR = 4.35; p = 0.033; CI 1.20, 11.20). Excess cancer incidence was noted for non-melanoma skin cancer (No. = 26; SIR = 1.59; p = 0.017; CI 1.10, 2.20), brain cancer (No. = 4; SIR = 3.45; p = 0.030; CI 1.20, 7.90) and Hodgkin's Disease (No. = 3; SIR = 4.54; p = 0.030; CI 1.20, 11.70). These findings, suggesting an excess risk for certain cancers in commercial airline pilots, are based on small numbers and need to be confirmed in larger cohort studies.

Aerospace Medicine↗

The effect of leucyl-leucine methyl ester on proliferation and Ig secretion of EBV-transformed human B lymphocytes.

The selective cytotoxicity of the lysosomotropic methyl esters of leucine or its lysosomal condensation product leucyl-leucine has been used to investigate the effect of cytolytic cells on the clonal outgrowth, cellular proliferation and antibody secretion of Epstein-Barr virus (EBV)-transformed human B cells. Large granular lymphocytes (LGL), monocytes, and a subset of T cells (CD8/CD11+) were permanently eliminated by the ester treatment. These lysosome-rich cells severely inhibit the clonal outgrowth of EBV-infected B cells, as determined by Poisson distribution calculations. Furthermore, leucyl-leucine methyl ester-treated and EBV-infected lymphocytes showed a significant increase in proliferative capability as well as immunoglobulin (Ig) production (three to 11 times) compared to non-treated but similarly infected lymphocytes. Since the effect of leucyl-leucine methyl ester treatment was also detectable in low-density (100 B cells/well) cultures, the suppression was unlikely to be exerted by EBV-specific T-cell clones, but pointed rather to the natural killer (NK) cells as effectors.

B-Lymphocytes↗

Cancer in relatives of retinoblastoma patients.

Medical histories with emphasis on malignant disease were obtained on 1,269 first and second degree relatives of 93 probands with retinoblastoma and on 671 first and second degree relatives of 50 age-matched control children. The number of nonocular malignancies expected to occur in first and second degree relatives of the probands were calculated using the observed number of neoplasms in control families as the standard. Using a Poisson distribution to evaluate the findings, a statistically significant excess of cancer was found in relatives of the probands with retinoblastoma. Gastrointestinal malignancies were particularly common in this population.

Cross-Sectional Studies↗

Chromosome aberrations in mixed cultures of in vitro irradiated and unirradiated human lymphocytes.

Human whole blood samples were exposed to different doses (1, 2, 4, 6 or 10 Gy) of gamma-radiation and mixed with different volumes of non-irradiated blood before culturing to simulate partial body irradiations. Chromosome aberrations were analysed and the frequency of dicentrics was found to be lower than expected, particularly when irradiated blood was mixed with large volumes of non-irradiated blood and after exposure to high radiation doses. For the mixtures of irradiated and unirradiated blood the deviation from the Poisson distribution depends on the respective proportions and on the doses. The results can be correlated to in vivo aberration frequencies in case of therapeutical treatments, but the yields of aberrations are generally underestimated in vitro.

Chromosome Aberrations↗

An evaluation of sampling methods within communities and the validity of parasitological examination techniques in the field.

In order to enable the assessment of schistosomiasis control, it has to be monitored. The methods and techniques employed for monitoring have to be validated in turn. In the Malian National Schistosomiasis Control Programme, only samples of the village population are examined. For practical and economic reasons, the sampling procedure is not free of bias from self-selection. When rates of samples are compared with results of examining the whole population no significant difference between the rates was found. Infection rates were precise to about +/- 5%. The sensitivity and specificity of laboratory technicians put to the task of identifying and counting the eggs of Schistosoma haematobium or S. mansoni in urine or stool samples differed considerably. The lowest scores were obtained by a laboratory technician from a district health centre who accompanied the central control team for a month. The predictive values of samples read positive dropped significantly below a general prevalence of 20%. The technician from the district centre would read samples falsely positive in more than 70%. However, the same person would read only 10% of slides falsely negative, once prevalence has dropped below the threshold of 20%, when maintenance depends on the performance of basic health services. The amount of stool used for a Kato-Katz preparation is only a 25th of one gram. The distinction between light and intensive infections with S. mansoni is therefore based on counting 1 to 3 or 4 or more eggs in a preparation. In a poisson distribution with mean 1, the difference between 1 and 4 is not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Seasonality comparisons among groups using incidence data.

A new test using incidence data is developed for testing whether two or more groups have the same seasonal pattern. The method fits sine waves to the data with a fundamental period of one cycle per year, and has the possibility of using higher harmonics, when necessary, to adequately model the data. The seasonal pattern can, therefore, have an arbitrary shape. The method allows for different length time intervals and different size populations at risk in the time intervals. Maximum likelihood estimation, based on the Poisson distribution, is used to determine the parameters of the model. Likelihood ratio tests and Akaike's information criterion (AIC) are used to determine the number of harmonics, and to test hypotheses. This method has been used to test for seasonal patterns in the incidence of insulin-dependent diabetes mellitus (IDDM) in Colorado among persons aged 0-17 years. Comparisons of seasonal patterns are made between males and females, and three age groups, each controlling for the other effect as in analysis of variance. Other potential applications of this approach are also discussed. A basic program is available for an IBM-PC to carry out these analyses.

Adolescent↗