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PubMed1993

Updated analyses of combined mortality data for workers at the Hanford Site, Oak Ridge National Laboratory, and Rocky Flats Weapons Plant.

Updated analyses of mortality data on workers at the Hanford Site, Oak Ridge National Laboratory (ORNL), and Rocky Flats Weapons Plant are presented with the objective of providing a direct assessment of health risks resulting from protracted low-dose exposure to ionizing radiation. For leukemia, the combined excess relative risk estimate was negative (-1.0 per Sv), and confidence limits excluded risks that were more than slightly larger than those forming the basis of ICRP recommendations. For all cancer except leukemia, the excess relative risk estimate was 0.0 per Sv, but confidence limits indicated consistency with estimates several times those forming the basis of ICRP recommendations. Of 24 cancer types tested, 12 showed positive correlations with radiation dose and 12 showed negative correlations, as would be expected by chance fluctuation. Cancer of the esophagus, cancer of the larynx, and Hodgkin's disease showed statistically significant correlations with radiation dose (P < 0.05), but these correlations were interpreted as likely to have resulted from bias or chance fluctuation. Evidence of an increase in the excess relative risk with increasing age at risk was found for all cancer in both Hanford and ORNL, and both populations showed significant correlations of all cancer with radiation dose among those 75 years and older. Although this age effect may have resulted from bias in the data, its presence suggests that risk estimates based on nuclear worker data be interpreted cautiously.

Adult↗

PubMed2007

Interval estimation for rank correlation coefficients based on the probit transformation with extension to measurement error correction of correlated ranked data.

The Spearman (rho(s)) and Kendall (tau) rank correlation coefficient are routinely used as measures of association between non-normally distributed random variables. However, confidence limits for rho(s) are only available under the assumption of bivariate normality and for tau under the assumption of asymptotic normality of tau. In this paper, we introduce another approach for obtaining confidence limits for rho(s) or tau based on the arcsin transformation of sample probit score correlations. This approach is shown to be applicable for an arbitrary bivariate distribution. The arcsin-based estimators for rho(s) and tau (denoted by rho(s,a), tau(a)) are shown to have asymptotic relative efficiency (ARE) of 9/pi2 compared with the usual estimators rho(s) and tau when rho(s) and tau are, respectively, 0. In some nutritional applications, the Spearman rank correlation between nutrient intake as assessed by a reference instrument versus nutrient intake as assessed by a surrogate instrument is used as a measure of validity of the surrogate instrument. However, if only a single replicate (or a few replicates) are available for the reference instrument, then the estimated Spearman rank correlation will be downwardly biased due to measurement error. In this paper, we use the probit transformation as a tool for specifying an ANOVA-type model for replicate ranked data resulting in a point and interval estimate of a measurement error corrected rank correlation. This extends previous work by Rosner and Willett for obtaining point and interval estimates of measurement error corrected Pearson correlations.

Confidence Intervals↗

PubMedDate not supplied

Prenatal measurement of the fetal cerebellum and cisterna cerebellomedullaris by ultrasound.

The fetal cerebellum can be visualized with ultrasound throughout the second trimester. We describe a technique for measuring the transverse and anteroposterior cerebellar diameters and the measurement of the cisterna magna in the same plane between 14 and 32 weeks gestation. Nomograms for these measurements against gestational age showed good correlation, and narrow confidence limits for the transverse cerebellar diameter. The transverse cerebellar diameter was also measured directly in 79 fetuses after midtrimester abortion and the measurements obtained were compared with the ultrasound TCD nomogram. Good correlation, was obtained between the post mortem measurements and the ultrasound TCD nomogram. Routine use of these measurements and nomograms should prove valuable in the diagnosis of congenital abnormality of the posterior fossa and may also be of use in assessing the effect of severe intrauterine growth retardation and other insults on cerebellar growth and development. The narrow confidence limits obtained with the TCD nomogram should enable it to be used with confidence in clinical practice.

Cerebellum↗

PubMed1990

Changes in plasma and whole blood lactate in response to arterial occlusion.

The development of lactic acidaemia in the adult forearm in response to partial and total arterial occlusion is described in both plasma and whole blood. Under conditions of total occlusion of the brachial artery lactate levels in the plasma compartment rise at a significantly faster rate; mean difference in gradients -11.6 95% confidence limits -15.6 and -7.6. Thus in these conditions they provide a more sensitive index of tissue hypoxia. Under conditions of partial occlusion there is no significant difference; mean difference in gradients 1.0 95% confidence limits 9.4 and -7.3. Though plasma lactate levels are more sensitive to the ischaemic state in certain circumstances, whole blood measurements are equally applicable to the monitoring of trends in blood lactic acid.

Acidosis, Lactic↗

PubMedDate not supplied

Influence of negative ultrasound findings on the management of in- and outpatients with suspected deep-vein thrombosis.

Real-time ultrasonography (US) was used as a single non-invasive method in the management of 174 patients (56 inpatients and 118 outpatients) with suspected deep-vein thrombosis (DVT). Therapeutic decisions were based on the results of ultrasonography alone. If the US examination was abnormal anticoagulant treatment was started. If the initial US examination was normal, no treatment was given and the patient underwent repeated testing and physical examination after 1 day, 7 days and 3 months. In the outpatient group, 1.3% of the ultrasonographic negative patients developed thromboembolic complications (95% confidence limits, 0.03-7.21%). None of the initial ultrasonographic negative patients developed proximal DVT after 1 day and 7 days. In the inpatient group, 10% of the ultrasonographic negative patients developed thromboembolic complications (95% confidence limits, 1.2-31.7%). In 18% of the ultrasonographic negative patients an alternative, unexpected diagnosis was obtained by ultrasound. The most frequent alternative diagnosis was a popliteal cyst. The results indicate that US alone appears to be a safe diagnostic method in the management of outpatients with suspected DVT. In the inpatient group further research is required for definite recommendations regarding a safe ultrasound follow-up schedule.

Adolescent↗

PubMed1987

Asbestos and renal adenocarcinoma: a case-control study.

A case-control study of renal adenocarcinoma has corroborated the hypothesis that asbestos is a cause of the disease. The odds of having been moderately or heavily exposed to asbestos 30 years before diagnosis were 45:473 among cases, whereas the comparable odds among controls were 26:492. A matched-pair analysis yielded an exposure odds ratio of 1.8 with 95% confidence limits of 1.1 and 3.1. After controlling for potential confounders and selection factors by means of logistic regression, the incidence rate ratio was estimated to be 1.6, with a one-sided 95% confidence limit of 1.0.

Adenocarcinoma↗

PubMed1985

The ventilatory response to carbon dioxide. An analysis of data obtained by the rebreathing method.

The ventilatory response to carbon dioxide using the rebreathing method was studied repeatedly in four healthy volunteers. The data were collected and processed in different ways using a microcomputer. Least squares linear regression analysis described the responses almost as accurately as a non-linear second-order polynomial regression. Linear regression analysis was undertaken on VI/PE'CO2 points, first breath-by-breath and then on three different groupings of breaths. The gradients and intercepts obtained by grouping agreed with those from breath-by-breath analysis both for a single response and for the mean result of a number of responses. Grouping tended to increase the correlation coefficient of a response, but widened the statistical confidence limits of the calculated gradient. The performance variability between repeated responses, the same no matter which data points were used, produced a range of gradients for each subject which was larger than the confidence limits on the gradient of a single response.

Adult↗

PubMed1982

Occupational bladder cancer and cigarette smoking in West Yorkshire.

This paper reports results from a case-referent study on bladder cancer being conducted in parts of West Yorkshire; 991 cases have been incorporated in the results to date. Overall there was a significant risk of bladder cancer associated with smoking cigarettes. This habit showed a risk ratio of 1.8 (95% confidence limits of 1.5-2.3) for males. In addition there were significant overall risks associated with certain occupations; these include process workers in the dye manufacturing industry, who had a risk of 2.9 (95% confidence limits of 2.0-4.3) for males. When smokers were contrasted with nonsmokers, however, the risk was 4.6 for dye manufacturing process workers who smoked, while for nonsmokers the risk was much less at 1.9.

Adult↗

PubMedDate not supplied

Atrial natriuretic peptide (ANP) as a stimulus of the human acrosome reaction and a component of ovarian follicular fluid: correlation of follicular ANP content with in vitro fertilization outcome.

Atrial natriuretic peptides (ANPs) from several species induced the human acrosome reaction. The maximal response was highest for human ANP (18.6% above unstimulated or baseline values) and decreased progressively for peptides derived from animals lower on the phylogenetic scale. ANP concentrations required for a half-maximal effect in noncapacitated spermatozoa ranged from 0.07 to 0.38 nM. ANP induced the acrosome reaction in capacitated spermatozoa, but the concentration required was higher than in noncapacitated cells. The response in noncapacitated spermatozoa was independent of added extracellular Ca2+ and was completely inhibited by 1 microM LY83583 (inhibits particulate guanylate cyclase). However, 10 microM N omega-nitro-L-arginine (inhibits soluble guanylate cyclase) had no effect. ANP (80 pM) and 3 microM 1,2-dihexanoyl-sn-glycerol each induced a nearly half-maximal acrosome reaction. Added in combination, they produced no increased response, suggesting antagonism. Follicular fluid had variable levels of immunoreactive ANP. Average ANP content was nearly zero in samples that contained no oocyte at the time of aspiration but was higher (6.9 pM; 90% confidence limits = 1.67-28.72 pM) in follicular fluid containing oocytes that did not fertilize in vitro. Highest concentrations of ANP were present in follicular fluid containing oocytes that fertilized in vitro (72.8 pM; 90% confidence limits = 38.1-139.1 pM). These data suggest that noncapacitated spermatozoa can acrosome react without added extracellular Ca2+ in response to an extracellular ligand. Also, human spermatozoa appear to contain receptors for ANP similar to those found in other cell types. The ANP content of follicular fluid might partly explain the ability of follicular fluid to induce the acrosome reaction.

Acrosome↗

PubMed1993

Ifosfamide, epirubicin and cisplatin (IEP): another active combination for small cell lung cancer (SCLC).

Sixty-four SCLC patients (44 males and 20 females, median age 60 years, median PS 60%) were treated with an IEP regimen. Forty-nine cases were evaluable, 35 cases were limited disease (LD) and 14 cases were extensive disease (ED). Treatment consisted of ifosfamide 1.5 g/m2 i.v. infusion for 4 h on days 1 and 2 with mesna uroprotection; epirubicin 60 mg/m2 i.v. on day 1; and cis-platin 60 mg/m2 i.v. infusion over 2 h on day 3; repeated treatment every 4 weeks. Eighty percent response rate (95% confidence limit = 66.75% to 93.25%) was seen in LD with 22.8% CR. In ED, total response rate was 85.7% (95% confidence limit = 67.36% to 104.04%) with 21.4% CR. One-year survival of LD was 45.5% and ED was 17.6%. Treatment toxicity was moderate. Most common toxic effects included alopecia, leukopenia (28.5% grade 3, 14.3% grade 4) nausea and vomiting (50% grade 2, 15% grade 3) and anemia (26.5% grade 3 and 4). Addition of thoracic radiotherapy after complete chemotherapy (only CR and PR in LD cases) was a good prognostic factor. These results suggest that IEP regimen is one of the active combination for SCLC. The dosage of IEP in this study caused moderate toxicity.

Adult↗

PubMed2000

Precise spatiotemporal repeating patterns in monkey primary and supplementary motor areas occur at chance levels.

Precise spatiotemporal patterns in neural discharge are a possible mechanism for information encoding in the brain. Previous studies have found that such patterns repeat and appear to relate to key behavioral events. Whether these patterns occur above chance levels remains controversial. To address this question, we have made simultaneous recordings from between two and nine neurons in the primary motor cortex and supplementary motor area of three monkeys while they performed a precision grip task. Out of a total of 67 neurons, 46 were antidromically identified as pyramidal tract neurons. Sections of recordings 60 s long were searched for patterns involving three or more spikes that repeated at least twice. The allowed jitter for pattern repetition was 3 ms, and the pattern length was limited to 192 ms. In all 11 recordings analyzed, large numbers of repeating patterns were found. To assess the expected chance level of patterns, "surrogate" datasets were generated. These had the same moment-by-moment modulation in firing rate as the experimental spike trains, and matched their interspike interval distribution, but did not preserve the precise timing of individual spikes. The number of repeating patterns in 10 randomly generated surrogates was used to form 99% confidence limits on the repeating pattern count expected by chance. There was close agreement between these confidence limits and the number of patterns seen in the experimental data. Analysis of high complexity patterns was carried out in four long recordings (mean duration 23.2 min, mean number of neurons simultaneously recorded 7.5). This analysis logged only patterns composed of a larger number (7-11) of spikes. The number of patterns seen in the surrogate datasets showed a small but significant excess over those seen in the original experimental data; this is discussed in the context of surrogate generation. The occurrence of repeating patterns in the experimental data were strongly associated with particular phases of the precision grip task; however, a similar task dependence was seen for the surrogate data. When a repeating pattern was used as a template to find inexact matches, in which up to half of the component spikes could be missing, similar numbers of matches were found in experimental and surrogate data, and the time of occurrence of such matches showed the same task dependence. We conclude that the existence of precise repeating patterns in our data are not due to cortical mechanisms that favor this form of coding, since as many, if not more, patterns are produced by spike trains constructed only to modulate their firing rate in the same way as the experimental data, and to match the interspike interval histograms. The task dependence of pattern occurrence is explicable as an artifact of the modulation of neural firing rate. The consequences for theories of temporal coding in the cortex are discussed.

Action Potentials↗

PubMed1998

Nonradioactive phosphopeptide assay by matrix-assisted laser desorption ionization time-of-flight mass spectrometry: application to calcium/calmodulin-dependent protein kinase II.

Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF) was used to quantify the phosphopeptide produced by calcium/calmodulin-dependent protein kinase II (CaMK II). MALDI-TOF measurements were performed in a linear and positive ion mode with delayed extraction excited at various laser powers and at different sampling positions, i.e., different loci of laser illumination. We find that the ratio of the peak area of the substrate (S) to that of its monophosphorylated form (SP) for a given mixture is constant, independent of the laser powers and/or of the sample loci illuminated by the laser. We also find that the fraction of phosphorylation determined by MALDI-TOF, or fMALDI-TOF, is proportionally smaller than that determined by HPLC, or fHPLC; the ratio fMALDI-TOF/fHPLC was 0.797 +/- 0.0229 (99% confidence limit, n = 7) for a 30-mer peptide substrate used in this study. A low mass gate, which turns off the detector temporarily, improved the ratio fMALDI-TOF/fHPLC to 0.917 +/- 0.0184 (99% confidence limit, n = 7). Our interpretation of this result is that the reduction of the phosphopeptide peak in the MALDI-TOF measurement is likely to be caused by a temporal loss of detector function rather than by a lower efficiency of ionization for the phosphopeptide compared with its parent species. In these measurements the experimental errors, up to the 50% phosphorylation state, were less than 5%. After an adjustment made based on the fMALDI-TOF/fHPLC ratio of 0.917, MALDI-TOF gave an accurate measurement for the kinetics of the CaMK II phosphorylation reaction. Since only a small volume of the reaction mixture, typically containing 3 to 50 pmol of substrate, is required for the MALDI-TOF measurement, this method can be adapted to a nonradioactive microscale assay for CaMK II and also for other protein kinases.

Amino Acid Sequence↗

PubMed2001

Acute terminal ileitis, yersiniosis, and Crohn's disease: a long-term follow-up study of the relationships.

Background: During the past decade, very little has been published on the relationships between Yersinia enterocolitica, acute terminal ileitis (ATI), and Crohn's disease, possibly due to a decrease in Yersinia infections and, consequently, in ATI. Methods: Fifty-three patients admitted to Herlev University Hospital during the period 1976-1998 were diagnosed as having ATI while undergoing surgery for suspected acute appendicitis. The patients were followed up, and both Yersinia titers and the development of Crohn's disease were registered. Results: Forty-four patients (83%) were tested for Yersinia, 17 of whom (39%; 95% confidence limits, 24-55%) were positive. The incidence of yersiniosis in ATI decreased significantly during the observation period (P<0.05), whereas the incidence of ATI itself was unchanged. Thirteen of the 53 patients (25%; 95% confidence limits, 14-38%) had, in addition to ATI, an inflamed appendix. Three patients developed Crohn's disease during a median observation period of 13 years (cumulative risk 6.1%). None of them had yersiniosis. Conclusions: The incidence of ATI remained stable during the observation period, even though the number of Yersinia infections decreased. This may have been due to an increase in gastrointestinal infections caused by other enteric pathogens. In accordance with previous findings, ATI patients who developed Crohn's disease did not have yersiniosis. Thus, it is still of prognostic value to test patients with ATI for Yersinia and perhaps for other enteric pathogens as well.

Journal Article↗

PubMed1986

Pneumococcal vaccine efficacy in selected populations in the United States.

The efficacy of pneumococcal vaccine in groups of patients in the United States at high risk for pneumococcal disease was estimated by comparing distributions of serotypes of Streptococcus pneumoniae isolated from vaccinated and unvaccinated persons. Between May 1978 and March 1984, 187 blood isolates and 62 cerebrospinal fluid isolates from vaccinated patients, and 1447 blood isolates and 191 cerebrospinal fluid isolates from unvaccinated patients were serotyped at the Centers for Disease Control. The study did not include patients who were less than 2 years old or who had Hodgkin's disease, multiple myeloma, or immunoglobulin deficiency. In patients with bacteremic disease, the overall efficacy of pneumococcal vaccine was estimated at 64% (95% confidence limits, 47% to 76%); efficacy did not differ significantly with age. In persons over 65 years of age with diabetes mellitus, chronic heart disease, pulmonary disease, or no underlying illnesses, efficacy was 61% (95% confidence limits, 1% to 85%). These findings support the use of pneumococcal vaccine in selected populations in the United States.

Adolescent↗

PubMed1975

[Toluidine blue staining in laryngeal diseases (author's transl)].

The authors present the results of 83 consecutive in vivo stainings with toluidine blue in various laryngeal diseases. Thirty one (86%) of the 36 malignant tumors showed positive staining. (95% confidence limits: 70-95.) It is concluded that malignant tumors will nearly always fix the dye, and that a negative staining test seems to be evidence against cancer. (Predictive value of negative test: 0.89, 95% confidence limits: 76-96.

Carcinoma in Situ↗

PubMed1988

Human immunodeficiency virus (HIV) antibodies in patients with haemophilia and other inheritable blood clotting disorders in south west Poland (Lower Silesia region).

In order to determine the frequency of HIV antibodies among patients with haemophilia and other inheritable blood clotting disorder in the Lower Silesia region of South-West Poland, we examined a representative fraction comprising 106 patients from a cohort of 302 blood clotting disorder patients. The methods used for detecting HIV antibodies were an ELISA, the immunoblotting test ("Western blot") and an indirect immunofluorescence test. 8 patients were reactive in the ELISA, but only 2 (1.9%) patients were truly seropositive by the confirmation tests. Both patients have received imported commercial factor VIII preparation. Totally 17 patients have been treated with imported factor VIII, thus 12% (95% confidence limits: 1.5-36.5%) of these were seropositive. This figure, which is lower than figures obtained from the USA and Western Europe, is probably due to far less intensive treatment of the patients. None (95% confidence limits: 0-4.1%) of the patients solely treated with blood transfusion and locally produced preparation was HIV antibody positive. These results indicate a low prevalence of HIV infection in this region of Poland but are, on the other hand, a strong argument for an introduction of HIV antibody screening of blood donors to maintain these favourable condition.

Acquired Immunodeficiency Syndrome↗

PubMed1994

[The caries occurrence in 7- to 12-year-old schoolchildren in Switzerland. The results of a country-wide survey 1987-89].

Between 1987 and 1989, a random sample of school children aged 7 and 12 years in Switzerland was drawn. In the first stage, districts were chosen. Within the districts, 12 children in the two specified age groups were selected. In addition, Switzerland was subdivided into two strata. The children of stratum 2 had consumed fluoridated salt since birth while those of stratum 1 had only done so during the preceding 4 to 5 years but had benefitted since the age of 5 to 7 from dental health education programs using fluorides at school. The oral examinations were carried out according to the methodology of the World Health Organization. Attendance was 94% (1115 children). 47% of the seven-year-old children were caries-free, and the average dmft was 2.20 (95% confidence limits at 1.87 and 2.52). The average dt was 1.06. These children had an average DMFT of 0.40, with 77% having DMFT = 0. At the age of 12, the average DMFT was 2.03, with confidence limits at 1.73 and 2.33. On average, they had 0.45 DT and 38% of them were caries-free (DMFT = 0). There were only minor differences between the 2 strata. These results agreed well with the data from 6 local surveys carried out during 1987 to 1989. When compared with the majority of European countries, caries experience of Swiss children was fairly low.

Age Distribution↗

PubMed1994

Aortic root replacement with pulmonary autograft in children.

Between September 1988 and February 1993, 14 patients whose ages ranged from 3 months to 16 years (mean 11.1 +/- 4.3 years) underwent replacement of the aortic root with the autologous pulmonary root for aortic valve disease. The follow-up was 4 years (cumulative total of 25.2 patient-years). There was no early mortality. Late mortality (one patient) was 7.1% (95% confidence limits 0% to 21%). This patient had juvenile rheumatoid arthritis and died of consequent congestive heart failure with autograft failure 6 months after operation. Event-free survival after 4 years was 78.6% (95% confidence limits 50% to 95%). One patient was reoperated on because of autograft failure caused by a relapse of rheumatic fever. One patient operated on for critical neonatal aortic stenosis has subnormal exercise tolerance because of restrictive cardiomyopathy and pulmonary homograft regurgitation. The other 12 patients were in New York Heart Association functional class I at the end of follow-up. There was no prevalence of bacterial endocarditis. There were no signs of primary structural degeneration of the pulmonary autograft. During follow-up, in eight patients, increased anulus diameter of the pulmonary autograft could be demonstrated by precordial two-dimensional echocardiography, suggesting growth of the autograft. Our experience shows that aortic root replacement with the pulmonary autograft can be done with low mortality and morbidity in children with aortic valve disease. The operation seems to be contraindicated in children with juvenile rheumatoid arthritis because of the risk of recurrence of rheumatic disease in the autograft. The pulmonary autograft has also been shown to be susceptible to recurrence of rheumatic inflammation in children with a history of acute rheumatic fever. Despite pulmonary autograft replacement of the aortic valve in infants with critical valvular aortic stenosis and endocardial fibroelastosis, clinical results may be poor. Growth of the autograft is suggested by echocardiographic follow-up. We consider aortic root replacement with the pulmonary autograft the procedure of choice in children who require aortic valve replacement.

Adolescent↗