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Survival after groin dissection for malignant melanoma.

Groin dissection was performed in 158 patients with malignant melanoma (superficial dissection, 76 patients; radical dissection, 82 patients). Of 63 patients with palpable nodes, 57 patients (90%) had histologic involvement. Of 93 patients with nonpalpable nodes, 31 patients (33%) had histologically positive nodes. The 5-year survival rate for patients with histologically negative nodes (n = 69) was 77%; the 5-year survival rate for patients with histologically positive nodes (n = 89) was 43%. The respective 5-year disease-free survival rates were 72% and 34%. Of 57 patients with palpable, positive inguinal nodes, 21 patients (37%) had involvement of the deep nodes. Of 31 patients with nonpalpable, histologic involvement of the inguinal nodes, six patients (19%) had or developed involvement of the deep nodes. One of two patients with uncertain clinical status of the nodes preoperatively had positive deep nodes. In prophylactic node dissection, frozen section of the inguinal group of the nodes does not provide a reliable method, because of sampling errors, in determining microscopic involvement of the nodes and in deciding whether a superficial or radical groin dissection is to be done. For patients with positive nodes the 5-year survival rate was 48% when only the inguinal group was involved and was 28% when both inguinal and deep nodes were involved; the respective 5-year disease-free survival rates were 39% and 20%. Survival after therapeutic groin dissection may partly depend on the thoroughness of the procedure. Patients who have positive, deep nodes and who are undergoing an incontinuity dissection of the inguinal, iliac, and obturator nodes have an appreciable 5-year survival rate.

Female↗

Information, discrimination and divergence in cytology. II. Total discrimination as a measure of performance.

Discrimination is the expectation of log odds ratios. Performance in diagnostic cytology, as compared to the results of histopathology or to a peer-reviewed consensus, can be measured by the total discrimination, which is a well-defined measure of information in information theory and test theory. The total discrimination, as a measure of performance, was calculated for the Gynecologic Cytology Laboratory of the University of Minnesota for the years 1985 through 1987, based on 3,545 sets of single-slide Papanicolaou smears and colposcope-directed biopsies. Similar calculations were made for the performances of physicians and technicians on peer-reviewed "clear-cut" Papanicolaou smears, as reported in a study from the Centers for Disease Control (CDC). For fair comparison of the two different sets of observations, the cytologic categories and corresponding histologic states were merged into five categories and states. The cytologic performance of our laboratory, tested against the histologic diagnoses, and the performances of the physicians and technologists tested against peer-reviewed check samples by the CDC were 0.53, 0.45 and 1.17 decits, respectively. These values generally agree with the conclusions derived by more conventional methods used by the CDC. When sampling errors of cytology specimens are taken into account, the performance of our laboratory, measured by the total discrimination of the cytology-histology confusion matrix, was approximately equal to the performance of the group of technologists studied by the CDC, which was in turn significantly better than that of the group of physicians studied by the CDC. This study demonstrates the value of using the total discrimination for quantifying the performance of a cytology laboratory, a cytopathologist or a cytotechnologist, without the arbitrary means usually used to evaluate such performances.

Colposcopy↗

Information, discrimination and divergence in cytology. IV. Quality control in diagnostic cytology.

The performance of diagnostic cytology on Papanicolaou smears can be periodically monitored by calculating the total discrimination or the total divergence of the cytologic diagnoses against the histologic diagnoses on samples obtained by colposcope-directed biopsies. Using these measures, the annual performances of the Gynecologic Cytology Laboratory of the University of Minnesota between 1980 and 1988 were retrospectively analyzed. For those years, the total discrimination and total divergence behaved similarly and were sensitive to the performance of the total system, including specimen sampling errors and laboratory precision. The lowest limits of the permissible range of the total discrimination and total divergence were 0.15 and -1.21 decits, respectively, for a single-slide Papanicolaou test if an 80% "hit" rate was accepted as the lowest threshold for each category. The optimal numbers of category-states were not a sensitive indicator of the quality of a laboratory; i.e., the optimal number of diagnostic categories remained at three throughout the period studied.

Female↗

Inflammatory atypia on cervical smears. A diagnostic dilemma for the gynecologist.

In light of the current controversy on the significance, follow-up and management of women with cervical smears showing "inflammatory atypia" (IA), a study was conducted to correlate the initial cytologic diagnosis of IA with the follow-up findings in colposcopically directed cervical biopsies and smears. From March 1988 through June 1989, 70 women had two consecutive smears reported as IA; all underwent colposcopy and cervical biopsy. In 58 patients (83%) the biopsies and smears obtained during colposcopy were negative for condyloma and/or cervical intraepithelial neoplasia (CIN). Ten patients (14%) had condylomas, and two (3%) had condylomas with CIN (one CIN I and one II). The initial IA smears from those 12 patients were reviewed retrospectively: 2 showed condylomas (they had been undercalled), 5 were "suggestive of condyloma" (the atypical cells were too few or poorly preserved for a definitive diagnosis), and 5 showed IA. None showed cytologic evidence of CIN, most probably because of sampling error. Our results suggest that colposcopy is warranted after two consecutive diagnoses of IA on cervical smears, considering that 17% of the patients in our study showed underlying intraepithelial lesions of the cervix.

Adolescent↗

Frozen-section analysis of allograft renal biopsy specimens. Reliable histopathologic data for rapid decision making.

Rapid tissue diagnosis during acute events associated with renal transplantation is often necessary to permit immediate decisions regarding initiation or modification of therapy. To achieve this, we performed frozen section analyses with cryoprotected alcoholic Bouin's-fixed tissue, which permits evaluation within 2.5 hours. During a 30-month period, 200 allograft biopsies were performed; 68 frozen sections were obtained when deemed necessary by the clinical team. We compared frozen-section diagnoses with those following regular evaluation of the biopsy specimen. Agreement in diagnoses occurred in 61 (88.4%) of 69 specimens. Acute rejection was the dominant diagnosis (n = 39); others were acute tubular necrosis, cyclosporine toxicity, chronic rejection, and infection. Major misdiagnoses included acute vascular processes (three capillary and/or venous thromboses and one vascular inflammation); acute cellular rejection was missed in two cases, reflecting a sampling error. Secondary diagnoses not of immediate therapeutic importance were detected in seven frozen sections and missed in nine. These included chronic glomerulopathies, nephrosclerosis, and mild chronic rejection. Although acute vascular phenomena may be difficult to recognize in frozen sections, we conclude that allograft biopsy frozen-section analysis is a valuable part of the care of transplant recipients.

Biopsy↗

The cytopathologic diagnosis of esophageal adenocarcinoma.

The diagnostic cytologic features were analyzed in 18 cases of histopathologically proven esophageal adenocarcinoma accessioned at the Johns Hopkins Hospital between 1975 and 1988 for which cytologic material was available. Primary esophageal adenocarcinoma was diagnosed in 15 of 18 cytologic specimens (83%); in 3 cases (17%), carcinoma was suspected, but the changes were nondiagnostic. The most consistent cytologic changes included both architectural features (loss of orientation and nuclear crowding) and criteria of malignancy (high nuclear/cytoplasmic ratios and prominent nucleoli). In the 15 diagnostic cases, the nucleoli were small in 8 and round in 11; in the majority of these cases, the nuclei contained one to three nucleoli. In addition, nuclear and cytoplasmic molding was seen in 9 of these 15 cases, hyperchromasia was present in 8, coarse chromatin clumps were seen in 5, and tissue fragments tended to be multilayered. Review of the three nondiagnostic cases showed that scant material was present in two; the third case had abundant material, but only nondiagnostic changes, suggesting a sampling error. Barrett mucosa was seen in 7 of the 18 cases. These cases show that esophageal adenocarcinoma can be reliably diagnosed on cytologic preparations, based on the consistent architectural features and the usual cellular criteria of malignancy.

Adenocarcinoma↗

Probability of transmission of Chagas disease by Triatoma infestans (Hemiptera: Reduviidae) in an endemic area of Santiago del Estero, Argentina.

The daily probability (P) of transmission of Trypanosoma cruzi to a noninfected human host by an infected Triatoma infestans bug was estimated using field data from a 2-year longitudinal study carried out in a rural settlement of 20 households in Amamá, Santiago del Estero, Argentina. The following information was used for this purpose: the bug density and the proportion of infected bugs; the bug biting rate and the distribution of bites between humans and animals; the age-specific seropositivity to T. cruzi of the human population; and the actual number of new cases of human infection. The 2-year accumulated number of infective contacts per house estimated using a binomial model shows a statistically significant logistic correlation with the observed proportion of new cases per house. An average house where new cases of human infection were registered in the 2-year period had a P value of 0.0012, while an average general house (i.e., with and without new cases) had a P value of 0.0009. The observed range of P is discussed in terms of the chain of factors that affects the individual human risk of acquiring the infection and the possible entomological sampling errors.

Adolescent↗

Differential diagnosis of integumentary and mucous membrane lesions. Neoplasia or inflammation?

Lesions occurring on the skin and mucous membranes of domestic animals often present both diagnostic challenges and diagnostic confusion. One of the most common causes of confusion is inflammatory lesions that can be mistaken for neoplasia and vice versa. This confusion may emanate from intrinsic biologic variability, histopathologic interpretation, secondary alterations subsequent to inflammation or necrosis, or sampling errors and omission of pertinent information by the clinician. Some diagnostic problems associated with diagnoses of granulomatous inflammation, mesenchymal neoplasia, mast cell tumors, and squamous cell carcinomas are presented, and selected specific differential diagnoses associated with diagnostic problems are discussed.

Animals↗

Thought disorder in the relatives of schizophrenics. A meta-analytic review of selected published studies.

Selected published studies investigating the existence of thought disorder in close relatives were re-examined in response to the conclusion by Saccuzzo, Callahan, and Madsen (J Nerv Ment Dis 176:368-371, 1988) that "the evidence for thought disorder in the families of schizophrenics is weak and inconclusive." A meta-analysis was performed on a subset of these studies to determine the (weighted) average effect size and its variability. The results indicated that the effect size was significant, i.e., there is a definite association between being related to a schizophrenic and manifesting (subclinical) thought disorder. Moreover, the variability of effect sizes among studies was not entirely due to sampling error and needs to be explained in terms of moderator variables.

Adolescent↗

[Occurrence of antigen-antibody complexes in the clinic].

We have analyzed 3,671 out of 16,000 immune-complex determination for this I.U.I.S.-Symposium in St. Georgen/Längsee, Carinthia, Austria. Patients came from various parts of Austria suffering from various inflammatory, regressive, autoimmune diseases or immunodeficiency. After extended trials of standardization with various complement tests and biological assays we have studied systematically PEG-precipitation and correlated with the clinic and biopsy in representative cases. Our experience showed, that complement assays may be sensitive to storage, shipping and sampling errors and have to be considered with this respect. Physical methods give additional informations to the diagnosis, prognosis and course of some diseases and are very useful for the clinical routine laboratory with the reservation, that the precipitated material consists of inflammatory and other denatured proteins but immunecomplexes. Precipitated materials is easily accessible to further biochemical identification.

Antigen-Antibody Complex↗

Characterization of the humoral immune response to genital papillomaviruses.

Human papillomaviruses (HPVs) have been detected in a wide range of proliferative lesions of squamous epithelium. A number of HPV types are associated with lesions of the genital tract. Some types (HPV types 6 and 11) are detected frequently in benign genital warts (condylomata acuminata); other types (HPV types 31, 33, 42 and others) are associated with dysplastic lesions of the uterine cervix; and certain HPV types (HPV types 16 and 18) are found in a high proportion of squamous cell carcinomas of the cervix and vulva. However, all of these HPV types have been detected also in normal epithelium. To date, investigators have relied primarily upon the detection of viral DNAs in clinical specimens as evidence of HPV infections. Such assays cannot determine whether past infections with HPVs have occurred which have subsequently resolved. Latent infections and current infections might also evade detection because of sampling errors or because of suboptimal sensitivity of DNA detection methods. Efforts to develop HPV serological assays have been hampered by the lack of appropriate viral antigens, since HPVs cannot be propagated in tissue culture and virions are not abundant in infected human tissues. Using HPV-encoded proteins expressed in Escherichia coli, we developed assays to measure human antibodies that react with HPV proteins. Human antibodies to late gene products (L1 and L2) of genital-type HPVs were more prevalent than antibodies to early gene products. However, approximately 15% of sera contained antibodies that reacted with the HPV16 E7-encoded protein, a gene product that has been implicated in HPV16-mediated cellular transformation. The human antibodies appeared to be type or "serotype" specific, because the antibodies did not cross-react with homologous proteins encoded by other HPV types. Antibodies to proteins encoded by HPV types 6 or 11 were detected in approximately 70% of adults, while antibodies to proteins encoded by HPV type 16 were found in approximately 50% of adults. Antibody prevalence was not associated with measures of sexual activity. There was also no significant difference between the prevalence of antibodies to HPV types 6 or 16 proteins in children when compared to the antibody prevalence in sexually active adults. These results suggest that infections by genital HPV types are widespread and frequently cause clinically inapparent infections. The viruses have a broad tropism for mucosal epithelium and are likely to be acquired by other modes, as well as by sexual transmission.

Antibodies, Viral↗

Automated differentials in the hematology laboratory.

The white blood cell differential continues to be one of the most widely performed clinical laboratory procedures. However, its clinical usefulness is affected by sampling error and, to some extent, by classification criteria. It is also labor intensive and expensive to perform. Automated leukocyte differential instrumentation addresses many of the sources of error that occur with the manual differential. Current state-of-the-art instrumentation will give results that equal or exceed the routine manual differential. Because these instruments also examine red blood cell and platelet parameters, as well as providing white blood cell information, they can better screen for significant abnormalities as well as greatly reduce the expensive and time-consuming manual differential procedures.

Automation↗

Fractionator studies on Purkinje cells in the human cerebellum: numbers in right and left halves of male and female brains.

Direct estimates of the numbers of Purkinje cell nucleoli in 22 aged human cerebella of known weight were obtained from paraffin-embedded sections using the fractionator. The nucleoli were counted in single sections. The estimates are unbiased by fixation, section thickness or sampling errors and are free from any assumptions about shape, size or spatial orientation. Left and right sides of the cerebellum were analysed in ten subjects whilst sex differences were examined in eleven subjects. No significant lateral differences in fixed weight or nucleolar number were observed. The group means (coefficients of variation) per side were 45 g (18%) and 7.8 millions (26%) respectively. The average complement of nucleoli in 22 cerebella amounted to 15.6 millions (22%). Estimated numbers did not show any significant correlation with cerebellar weights and, in a subsample of these brains (five male and six female), apparent sex differences were not significant.

Aged↗

Combined utility of gene rearrangement analysis and flow cytometry in the diagnosis of lymphoproliferative disease in the bone marrow.

The diagnosis of lymphoma involving bone marrow is often complicated by the presence of nonspecific lymphoid aggregates. Morphologic criteria may not permit the distinction of benign from malignant lymphoid aggregates with certainty in all cases. We combined morphology with immunophenotypic and immunogenotypic analyses of aspirated marrow cells to develop more reliable criteria for the diagnosis of marrow involvement by lymphoma. The presence of morphologically recognizable lymphoma cells in the bone marrow aspirate was always confirmed by immunogenotypic analysis. The yield of either immunophenotypic or immunogenotypic analyses on morphologically negative marrows was very low. Focal paratrabecular involvement by lymphoma was not always confirmed by immunophenotypic or immunogenotypic analyses, probably due to sampling error and factors interfering with aspiration of the lymphoid aggregates. Thus, the immunologic and molecular studies supported, but did not substantially improve upon the morphologic criteria that are in common usage for distinguishing benign from malignant lymphoid aggregates in the bone marrow. Finally, evidence of B-lymphocyte clonality was obtained in four of five cases in which there were nonspecific lymphoid aggregates in the bone marrow in the absence of otherwise clinically definable malignancy.

Aged↗

[Quantitative analysis of low concentrations of cristobalite in thin layers by x-ray diffraction].

A new x-ray diffraction procedure for the determination of cristobalite in the presence of amorphous silica is described. The standards are obtained by deposition of thin layers of watery suspensions of cristobalite and amorphous silica mixtures on silver or lead disks or cellulosa filters. Six calibration curves are then calculated to reduce weight and sampling errors. Six mcg of cristobalite mixed with 594 mcg of amorphus silica is the lowest detectable limit. The method may be used for the analysis of both raw materials and respirable dust.

Air Pollutants↗

Accuracy of frozen section diagnosis in soft tissue tumors.

This study was undertaken to analyze the accuracy of frozen section (FS) diagnosis of 118 soft tissue tumors with respect to the reasons for which the intraoperative consultation was indicated. Fifty-seven frozen sections were performed for the diagnosis of an unknown pathologic process. Complete agreement was established in 40.3% and the correct pathologic process in 43.9%, the diagnosis was deferred in 14%, and the remaining 1.8% were diagnosed incorrectly. Examination for determination of the adequacy of resection margin (22 cases), lymph node or skip metastases (23 cases), residual or recurrent tumor after previous surgery (29 cases), viable tumor tissue after previous locoregional or systemic therapy (ten cases), and identification of the specimen (five cases) proved to be 95.5%, 95.7%, 96.6%, 90%, and 100% accurate. Considering the whole series, an erroneous answer to a question posed by a surgeon was given in four cases (two false positive and two false negative), of which two cases were a sampling error made by pathologist. Intraoperative consultation by FS in soft tissue tumors is (a) reliable for general rather than exact diagnosis in defining the previously unknown pathologic process and (b) mandatory in evaluating resection margins and any discrepancies between preoperative cytologic and intraoperative gross impression.

Diagnostic Errors↗

Dilemma of variety of histopathologic grading systems for acute cardiac allograft rejection by endomyocardial biopsy.

From the International Society for Heart Transplantation Registry, it can be seen that more than 2000 hearts are now being transplanted per year and that this number is likely to continue to rise. Because the leading causes of death in the first year after heart transplantation are infection and acute rejection, it is clear that the problem of managing heart recipients becomes that of correctly diagnosing acute rejection. For many years the endomyocardial biopsy has provided a safe, reliable, morphologic index of acute rejection. Notwithstanding the drawback of an invasive technique and sampling error, the endomyocardial biopsy has prevailed as the single most reliable method for diagnosing acute rejection. In 1974 a grading system for the diagnosis of acute rejection from biopsy material was first described. Since then, the grading system has been updated, and over the years many different grading systems have evolved to accommodate better the style of managing heart recipients in different centers worldwide. Although this is satisfactory for individual centers, it has become clear that there is difficulty in comparison of different treatment regimens from transplant centers using different grades. For continued improvement of survival in heart recipients, multicenter trials using different treatment and management protocols must be tried. To accomplish this, direct comparisons between one regimen and another must be made. For this purpose, a universal grading system has been suggested. This article makes an initial attempt to point out the weaknesses and strengths of the current grading systems and an initial attempt to define the criteria that would be accepted in a universal, or standard, grading system.

Biopsy↗

Prognostic factors in atopic dermatitis.

A long-term follow-up study (24 years minimum) was made of 955 individuals aged 24-44 years, who had atopic dermatitis (AD) in childhood. The material was divided into two groups; patients who in 1952-56 had been hospitalized on at least one occasion at the Department of Dermatology, Karolinska Hospital, Stockholm (Group 1), and patients who in 1955-56 had been out-patients in the same department (Group 2). At the time of investigation 62% and 40% of the patients in Groups 1 and 2 respectively had ongoing dermatitis, the majority with mild skin lesions. The frequency of healing of AD and severity of persistent or recurring dermatitis were influenced by several factors. In order of relative importance, disregarding sampling errors, persistent dry/itchy skin in adult life, widespread dermatitis in childhood, associated allergic rhinitis, family history of AD, associated bronchial asthma, early age at onset, and female sex were associated with low frequency of healing and increased severity of persistent or recurring dermatitis.

Adolescent↗