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PubMed2002

Factors predicting disease outcome in early stage adenocarcinoma of the uterine cervix.

CONTEXT: Adenocarcinoma (AC) and adenosquamous carcinoma (ASC) comprise the second principal histological types of cervical carcinoma. As compared with the squamous cell cancer (SCC), these lesions are far less frequent, and their epidemiology, natural history and prognostic determinants are less well understood. OBJECTIVE: Patients with an early stage AC of the uterine cervix diagnosed in our clinic were subjected to detailed analysis for the prognostic determinants. STUDY SUBJECTS: A series of 94 women with early stage (adenocarcinoma in situ (AIS) to IIB) cervical ACs or ASCs diagnosed and treated in our department during 1995-1999 and subsequently followed-up for a mean of 43.1 +/- 16.2 (S.D.) months. MAIN OUTCOME MEASURES: Patients were examined by colposcopy, Papanicolaou (PAP) smear and biopsy. The stage of the disease (FIGO) and tumour histology in operative specimens were recorded, and univariate (Kaplan-Meier) and multivariate survival analysis (Cox) were run to explore the factors predicting disease outcome. RESULTS: Mean age of the women was 44.2 +/- 2.5 (S.D.) years (range 24-81 years), which is significantly (P=0.000) lower than that (49.9 +/- 14.2) of 464 SCC patients in our material. Minority of the women (38.2%) reported any clinical symptoms, but these correlated with the stage (P=0.041). Screening history was acceptable (i.e. screening interval 3 to 4 years) in 56 women, whereas 28 (29.8%) had no previous PAP smear taken. Interpretation errors were established in 17 (23.6%) and sampling errors in 6 (8.3%) of the 72 smears available for re-screening. No colposcopic lesions were found in 29 (30.9%) women. Follow-up data were available from 72 patients, of whom the disease progressed in four (one died), whereas 68 patients are alive and well at the moment. Patient's age (P=0.000), screening history (P=0.0127), FIGO stage (P=0.001), mode of therapy (P=0.0187), and presence of co-existent squamous cell lesions (P=0.0184) were significant prognostic indicators in univariate survival analysis. Cox's multivariate survival analysis disclosed FIGO stage (P=0.001) and screening history (P=0.006) as the only significant independent predictors of the disease outcome. CONCLUSIONS: The present data emphasise the importance of early cervical AC as a disease of younger women, making early detection of its precursors (AIS) by regular PAP smear screening mandatory in prevention of disease progression. This can only be achieved by increasing the sensitivity of the PAP smear in detecting abnormal glandular cells in asymptomatic women.

Adenocarcinoma↗

PubMed1988

Stability of arterial concentrations during continuous inhalation of C15O2 and 15O2 and the effects on computed values of CBF and CMRO2.

Stability of arterial whole blood and plasma concentrations is a basic requirement in the application of the oxygen-15 (15O2) steady-state inhalation technique for measuring regional cerebral blood flow and oxygen use. The level of stability obtainable in practice is reported in the form of retrospectively analysed blood data from 626 consecutive studies in patients with a range of clinical conditions. Serial arterial whole blood and plasma concentrations were measured during both C15O2 and 15O2 inhalations, and coefficients of variation were calculated. In addition, these concentrations were compared with the corresponding values recorded at the start of each study and maximum variations were calculated. For all four concentrations, mean and median coefficients of variation were around 5 and 4%, respectively. Mean and median maximum variations were around 9 and 7%, respectively. The effects of these variations on the calculations of regional cerebral blood flow, oxygen extraction, and oxygen use were estimated. Mean expected errors were found to be between 4 and 9%, and median expected errors between 3 and 6%. Inherent blood sampling errors were assessed from blood volume studies using 11CO-labeled red cells. These errors were found to be less than 3%.

Arteries↗

PubMed1999

Management of nonspecific low back pain by physiotherapists in Britain and Ireland. A descriptive questionnaire of current clinical practice.

STUDY DESIGN: A descriptive questionnaire of chartered physiotherapists. OBJECTIVE: To investigate current physiotherapeutic management of low back pain throughout Britain and Ireland. SUMMARY OF BACKGROUND DATA: Physiotherapists play a key role in low back pain management. Although clinical guidelines for best practice have been developed recently, there has been no large-scale attempt to describe current physiotherapeutic treatment approaches within Britain or Ireland. METHODS: After semi-structured interviews (n = 6) and two pilot studies (n = 77) were done, postal questionnaires were distributed to four regional cluster samples of the membership of two physiotherapy professional organizations (n = 2654). After two mailings, a random sample of 90 nonresponders were followed up. Data were analyzed using the Statistical Package for the Social Sciences (SPSS Ltd., Woking, Surrey, UK), and precision of the survey estimates was assessed by calculation of sampling errors and intraclass correlation coefficients for cluster sampling. RESULTS: Results were received from 1548 therapists (total response rate, 58.3%); of these, 813 reported that they were practicing in settings in which they treated patients with low back pain. Analysis of the results indicated the overall popularity of the Maitland mobilization and McKenzie approaches among physiotherapists. Although exercise per se was mentioned frequently by respondents, a marked difference in opinion among therapists regarding the optimal type of exercise for low back pain was obvious. Little evidence was demonstrated of the use of manipulation, fitness programs, or multidisciplinary efforts involving behavioral and physical aspects of treatment. Commonly used methods of electrotherapy were interferential therapy, ultrasound, pulsed short-wave diathermy, and transcutaneous electrical nerve stimulation. CONCLUSIONS: The results of this study emphasize the need to evaluate further and improve the dissemination of findings regarding the effectiveness of specific physiotherapy approaches for low back pain management.

Adult↗

PubMed1997

An estimation of the size distribution of amalgam particles in dental treatment waste.

Regulations have been adopted in several countries of the European Union which prescribe that dental treatment waste water must be discharged via an amalgam separator device. Since the effectivity of the device strongly depends on the size of the amalgam waste particles, this size was evaluated in waste water samples from eight dental offices. Per sample, all solid particles were separated from the waste water by pressure filtration, then dried and divided into six fractions by being sieved over five sieves with decreasing mesh width. Of the particles in each fraction, the density was determined by picnometry, the mass by weighing, and the area and width by image analysis. For this analysis, width was defined as the dimension perpendicular to the length of the particles. By combining the density, area, and width determinations of all fractions, we obtained mass distributions per waste particle width of the samples. The proportional amalgam mass of the distributions was estimated with the measured density of the particle fractions and with a number of assumptions for the density of amalgam particles only and of other waste particles only. Each waste sample has its own characteristics with respect to the mass and density of the particle fractions. The size distribution of waste particles has a bimodal shape and consists of a distribution of small (width, 2 to 90 microns) and large particles (width, 160 to 5500 microns). For small particles with a width up to 60 microns, the influence of the assumptions on the estimation of the proportion amalgam of the waste mass distribution is minor when compared with the sampling error. By averaging the estimations over the samples, one can estimate the weight of amalgam particles with a width < 10 microns and < 50 microns, respectively, between 4 and 15% and between 15 and 30%. The smallest particles comprising 5% of the amalgam mass have an estimated width of up to 15 microns.

Dental Amalgam↗

PubMed1991

Accuracy of breast frozen section diagnosis in the community hospital setting: a detailed analysis of 628 cases.

The author presents a detailed analysis of 628 breast frozen sections performed at Columbia Hospital over a 35-month period. These 628 frozen sections came from a total of 574 females and 13 males (mean age 55.3 years and range 20.1 to 95.0 years). Frozen section diagnosis was deferred in 18 cases (2.8%) and diagnostic accuracy for presence or absence of malignant neoplasia was 99.2%; one false positive case (pathologist judgement error) and four false negative cases (two sampling errors and two pathologist judgement errors) were detected. Strict diagnostic accuracy for this series was 98.7%. Fifty-three of 223 positive frozen sections (23.8%) were immediately followed by completion mastectomy. The author discusses the philosophy of frozen section technique and concludes that breast frozen section analysis in a busy community hospital setting can meet and even exceed the accuracy level attained at large academic medical centers.

Adult↗

PubMed1982

Paired cervical smears: a method of reducing the false-negative rate in population screening.

Cervical smears taken by the wooden Ayre spatula (widely used in the United Kingdom) and by a plastic spatula (Armovical) were compared for their ability to detect dysplastic cervical epithelium and endocervical cells. At the same time, the value of taking duplicate smears was assessed. Paired cervical smears were obtained at a single attendance from 21,352 women, using the 2 types of spatulas in 4 different sequences. Although individually the Armovical proved superior to the Ayre spatula for the collection of endocervical epithelial material, this advantage was not complemented by any marked improvement in its detection of cervical dysplasia. Paired smear sampling, however, was clearly more rewarding in this respect and also allowed the introduction of laboratory quality control, as each preparation of any given pair was examined by a different screener. The false-negative rate was 18.5%: it comprised 11.1% sampling error and 7.4% screening error. It is concluded that paired smear sampling in population screening would significantly reduce the false-negative rate.

Carcinoma in Situ↗

PubMed1987

Problems with measurements caused by high concentrations of serum solids.

There have been numerous reports of spectrophotometric and volume problems caused by elevated levels of lipids in blood. The offending lipids, primarily triglycerides, not only cause turbidity leading to optical aberrations when added to analytical reagents, but also result in short-sampling errors leading to the measurement of inaccurate volumes of sample. Numerous methods have been developed to clear the lipemia, including ultracentrifugation organic solvent extraction, chemical precipitation and, most recently, enzymic hydrolysis. Although the latter procedures eliminate the optical problems, they do not deal with the volume dilution error created by the triglycerides. In turn, corrective mathematics have been developed to compensate for the inaccurate pipetting caused by the elevated lipids in a sample; however, these empirical calculations are not truly accurate at high concentrations of total lipids. This monograph will describe the problems caused by the presence of elevated lipids and the means available for treating them.

Blood Chemical Analysis↗

PubMed1992

Detection of cytomegalovirus (CMV) in granulocytes by polymerase chain reaction compared with the CMV antigen test.

To compare the sensitivity and suitability of detection of active cytomegalovirus (CMV) infection by using monoclonal antibodies against CMV antigen (antigen test to detect antigenemia) and the polymerase chain reaction (PCR; to detect viral DNA) in granulocytes, 19 heart and 2 lung transplant recipients were closely monitored by these tests for at least 3 months after transplantation. All patients were CMV seropositive or had a seropositive donor. In total, 201 samples were tested; 46 were positive by both tests, 9 samples showed only antigenemia, 54 samples were positive by PCR only, and 102 samples were negative by both tests. PCR was positive earlier after transplantation in eight patients, whereas antigenemia was positive earlier after transplantation in one patient. In another four patients, both tests were positive at the same time. PCR was, on average, positive for a longer period of time. Discordant results showing a positive antigen test and a negative PCR were partly due to sampling error; some were positive by PCR on retesting. Samples which were negative by the antigen test and positive by PCR were taken at the beginning or at the end of an active CMV infection. In two patients, no active CMV infection was detected by the antigen test, cultures of urine and saliva, or serology, although PCR was positive for a long period of time in the two patients.

Antigens, Viral↗

PubMed2000

Comparison of patient age with MR imaging features of gangliogliomas.

OBJECTIVE: The purpose of this study was to compare MR imaging features of gangliogliomas in children less than 10 years old with those seen in patients at least 10 years old. MATERIALS AND METHODS: Our study population consisted of 15 female patients and 10 male patients with a mean age of 20 years. The early childhood group was composed of six children with a mean age of 5.5 years. The older group was composed of 19 patients with a mean age of 25.6 years. We assessed tumor volume, tumor location, percentage of tumor that was cystic, pattern of contrast enhancement, and degree of edema. RESULTS: The temporal lobe was the most common tumor location in both groups. Mean tumor volume in the early childhood group was 83 cm3, which was significantly larger than the mean tumor volume (9.78 cm3) for the older group (p = 0.001). Cystic tumors were more common in the early childhood group (83%) than in the older group (63%), and the average percentage of cysts in the cystic tumors was much higher in the early childhood group (67%) than in the older group (30%). Contrast enhancement was seen in five of six early childhood tumors and 13 of 16 tumors in older patients. Four of six tumors in the early childhood group and five of 19 tumors in the older patient group had associated edema. CONCLUSION: The mean tumor volume of gangliogliomas in the early childhood group was significantly larger than that of the older patient group. This finding may be indicative of differences in tumor growth patterns in the two groups, ability of the hemicranium to adjust to mass effect in childhood, or sampling error as a result of a relatively small sample size.

Adolescent↗

PubMed1989

Use of a laser diffraction particle sizer for the measurement of mean diameter of multicellular tumor spheroids.

Increasing use is being made of tumor cell lines cultured as cell aggregates (generally referred to as multicellular spheroids) in in vitro radiosensitivity and/or chemosensitivity tests. Conventional procedures for the determination of mean spheroid diameters for the construction of growth delay curves employ a microscope-image analyzer. However, this approach can prove excessively time consuming when large numbers of samples have to be measured. We have, therefore, been exploring the use of a Laser Diffraction Particle Sizer, the Malvern 2600 long bench model, for the measurement of mean spheroid diameter and size distribution. We report here a direct comparison between measurements carried out by the instrument and under the microscope. Also a comparison of growth curves for six cell lines constructed from measurements by the microscope and by the instrument. A number of factors that might affect the accuracy of spheroid diameter measurement by the instrument have been investigated: The effect of stirring to maintain the spheroids in suspension during measurement. Sampling error due to removal of a series of spheroid samples from culture flasks for measurement. Optimum numbers of scans to be carried out by the instrument to reach a constant value for mean diameter, and minimum SE of the mean.

Animals↗

PubMed2000

Comparison between anopheline mosquitoes (Diptera: Culicidae) caught using different methods in a malaria endemic area of Papua New Guinea.

The mosquito sampling efficiency of CDC (Centers for Disease Control) miniature light traps hung adjacent to mosquito nets, was compared with that of both indoor and outdoor human-bait collections in ten villages in the Wosera area of Papua New Guinea. The most frequently collected anopheline in the matched indoor and light trap samples was Anopheles koliensis Owen, followed by A. punctulatus Dönitz, A. karwari (James), A. farauti Laveran (sensu lato), A. longirostris Brug and A. bancroftii Giles. All species were much less frequent in the light traps than in landing catches. The hypothesis that the numbers of mosquitoes in light traps are proportional to human landing catches was examined using regression models that allowed for sampling error in both entomological measurements. Light traps under-sampled A. punctulatus and A. farauti s.l. at high densities. The models indicated that the ratio of light trap to landing catch females of A. koliensis and A. karwari increased with increasing mosquito density. Light trap catches of A. longirostris were proportional to indoor landing rates but when outdoor landing rates were high this species was under-sampled by light traps. Numbers of A. bancroftii in light traps were found to be proportional to those in outdoor landing catches, but were negatively related to those attempting to bite indoors. Circumsporozoite positivity rates for both Plasmodium falciparum Welch and P. vivax (Grassi & Feletti) in A. punctulatus and A. farauti s.l. were significantly higher in light trap collections than in either indoor or outdoor landing catches, suggesting that light traps may selectively sample older mosquitoes of these species.

Animals↗

PubMed1988

Estimation of allele frequencies at isoloci.

In some polyploid animals and plants, pairs of duplicated loci occur that share alleles encoding proteins with identical electrophoretic mobilities. Except in cases where these "isoloci" are known to be inherited tetrasomically, individual genotypes cannot be determined unambiguously, and there is no direct way to assign observed variation to a particular locus of the pair. For a pair of diallelic isoloci, nine genotypes are possible but only five phenotypes can be identified, corresponding to individuals with 0-4 doses of the variant allele. A maximum likelihood (ML) approach is used here to identify the set of allele frequencies (p, q) at the individual gene loci with the highest probability of producing the observed phenotypic distribution. A likelihood ratio test is used to generate the asymmetrical confidence intervals around ML estimates. Simulations indicate that the standard error of p is typically about twice the binomial sampling error associated with single locus allele frequency estimates. ML estimates can be used in standard indices of genetic diversity and differentiation and in goodness-of-fit tests of genetic hypotheses. The noncentral chi 2 distribution is used to evaluate the power of a test of apparent heterozygote deficiency that results from attributing all variation to one locus when both loci are polymorphic.

Alleles↗

PubMed1998

The uncertainty associated with the predictive value of test results.

The uncertainty associated with predictive value of test results was taken into consideration, as concerns both sampling error (related to the size of the statistical reference samples) and analytical imprecision (unavoidably involved by the measurement itself). A software package, developed for the statistical calculations, was used for the treatment of the results obtained for serum free thyroxin in euthyroid and dysthyroid subjects, assumed as an experimental model. Examples are shown for the obtainable functions predictive value vs. estimate and the related uncertainty regions. These data could help in comparing test results and, in particular, in preparing fully informative laboratory reports. The difficulties involved by an extensive application of the procedure are discussed.

Humans↗

PubMedDate not supplied

Platinum levels and clinical responses of tumours treated by cisplatin with and without concurrent hyperthermia: a case study.

The heterogeneity of platinum distributed within tissue after clinical administration of cisplatin was evaluated for the first time. Platinum levels were correlated with the observed clinical responses of separate superficial histiocytic sarcomas located in the forearm of a 74-year-old male patient. One of four lesions received four weekly treatments with hyperthermia administered concurrently with 30 mg/m2 cisplatin, while three lesions were treated with cisplatin alone. The lesion receiving hyperthermia concurrently with cisplatin had a solid partial response during a 6-week period following this therapy, whereas two other tumours receiving cisplatin alone progressed. One lesion could not be clinically evaluated. Platinum levels were determined in multiple samplings from three of the four lesions and normal tissue in order to evaluate the validity of taking a single tumour sample of 100 mg or less for the analysis of platinum content. Such a small single sample might provide a value significantly different from the true average because of sampling error. The range in platinum distribution encompassed an average of three-fold difference within eight separate sample groups, with a factor of six being the greatest difference in a single sample group. This degree of heterogeneity is great enough to suggest that conclusions made from the analysis of small and single random tissue samples could be sufficiently in error to misdirect investigative or medical decisions.

Aged↗

PubMed1998

Estimating sample size for epidemiologic studies: the impact of ignoring exposure measurement uncertainty.

Sample size requirements for epidemiologic studies are usually determined on the basis of the desired level of statistical power. Suppose, however, that one is planning a study in which the participants' true exposure levels are unobservable. Instead, the analysis will be based on an imprecise surrogate measure that differs from true exposure by some non-negligible amount of measurement error. Sample size estimates for tests of association between the surrogate exposure measure and the outcome of interest may be misleading if they are based solely on the anticipated characteristics of the distribution of surrogate measures in the study population. We examine the accuracy of sample size estimates for cohort studies in which a continuous surrogate exposure measure is subject to either classical or Berkson measurement error. In particular, we evaluate the consequences of not adjusting the sample size estimation procedure for tests based on imprecise exposure measurements to account for anticipated differences between the distributions of the true exposure and the surrogate measure in the study population. As expected, failure to adjust for classical measurement error can lead to underestimation of the required sample size. Disregard of Berkson measurement error, however, can result in sample size estimates that exceed the actual number of participants required for tests of association between the outcome and the surrogate exposure measure. We illustrate this Berkson error effect by estimating sample size for a hypothetical cohort study that examines an association between childhood exposure to radioiodine and the development of thyroid neoplasms.

Adolescent↗

PubMedDate not supplied

Immunocytochemical detection of p16INK4a protein in scraped cervical cells.

OBJECTIVE: To develop an immunocytochemical technique for p16INK4a protein detection in scraped cervical cells for cancer screening. STUDY DESIGN: We took duplicate cervical scrapes from each participant, the first for a Pap smear and the second for p16INK4a protein detection. From a 50-microL cell suspension prepared from the scrape rinsing, a 10-microL aliquot was dropped in a 5-mm-diameter circle on a glass slide, air dried and fixed in 0.1% formal saline (1 hour) and in 95% ethanol (10 minutes). Using the immunocytochemical technique, slides from 30 samples of each Pap diagnosis class were stained sequentially with mouse monoclonal anti-p16INK4a (primary antibody), biotinylated goat antimouse IgG (secondary antibody), horse-radish peroxidase-labelled streptavidin and 3,3'-diaminobenzidine and mixed hydrogen peroxide, then counterstained with hematoxylin. A positive sample had to contain > or = 3 immunoreactive cells. Results were confirmed by western blot analysis of lysates from the remaining 40 microL of each cervical cell suspension. RESULTS: Samples were grouped as control (normal cervical cells), mild dysplasia (ASCUS, LSIL) and high abnormality (HSIL, SCC). Using the immunocytochemical technique, > 95% of the positive (SiHa cells) but 0% of the negative controls (human embryonic lung fibroblast cells) showed immunoreactive cells. All slides displayed a clear background without mucus, and positive cells were stained in both the cytoplasm and nucleus. p16INK4a Protein was detected in 17 of 30 (56.67%) ASCUS and 10 of 30 (33.33%) LSIL and increased with the degree of abnormality to 93.33% (28 of 30) and 96.67% (29 of 30) in the HSIL and SCC group, respectively. Normal cervical cells and degenerated malignant cells were nonimmunoreactive. Western blot analysis confirmed similar positive samples in the low-abnormality group, while the whole high-abnormality group was immunoreactive. A sampling error might have caused the 2 HSIL and 1 SCC sample to be negative using our immunocytochemical technique. CONCLUSION: p16INK4a Protein detection in scraped cervical cells using the immunocytochemical technique correlated with western blot analysis and was nontraumatic and precise. It offers a significant diagnostic adjunct to the Pap test for cervical cancer screening.

Biomarkers, Tumor↗

PubMed1989

Sources of diagnostic error in fine needle aspiration of the thyroid.

Smears obtained from 795 patients with suspicious thyroid nodules by fine needle aspiration (FNA) of the thyroid gland were seen over a 5-year period at the UCLA Center for the Health Sciences. From 72 patients who underwent subsequent surgical excision of their nodules, inadequate or discrepant FNA diagnoses were noticed in 20 cases (27.8%). These errors could be attributed to inadequate material for diagnosis (n = 6), sampling errors (n = 2), and cytodiagnostic errors (n = 12). If the diagnosis of follicular neoplasm was treated as indeterminate for malignancy, the overall efficiency of FNA was 88.9%. All false-negative diagnoses were related to procedure (i.e., inadequate smears or missed sampling of the lesion). The frequency of inadequate smears, in turn, was strongly related to the type of physician performing the aspiration. The frequency was highest among community-based clinicians (32.4%) and lowest among hospital-based cytopathologists (6.4%). With adequate sampling, the finding of 100% sensitivity in the diagnosis of malignant neoplasms by FNA cytology reaffirms its role as the procedure of choice in the initial screening of thyroid nodules.

Adolescent↗

PubMed2003

The Effect of altering ADL thresholds on active life expectancy estimates for older persons.

OBJECTIVES: Research on disability and active life expectancy (ALE) has often criticized the measurement of disability but has rarely empirically investigated the effect of changing measurement. The purpose of this study was to determine whether altering the number of activities of daily living (ADLs) required to consider an individual "disabled" affects population-based ALE estimates after considering parametric uncertainty and sampling error. METHODS: The authors develop a Bayesian approach to estimating multistate life tables for a three-dimensional state space, using data on community-dwelling older adults from the 1989 and 1994 National Long Term Care Survey analytic files. Empirical confidence intervals for ALE are compared across 6 models using successively higher ADL cutoffs for defining individuals as being disabled. RESULTS: After considering sampling and other errors in the estimation of transition probabilities, the authors found that altering the threshold for measuring disability has relatively little effect on ALE estimates, especially with higher ADL-level thresholds and at older ages. DISCUSSION: The implications of the results include that disability measurement, including altering the definition of being disabled and possibly expanding the state space of a model, may not affect population-based estimates of ALE.

Activities of Daily Living↗