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PubMed1983

Effect of exercise on QRS duration in healthy men: a computer ECG analysis.

Increased sympathetic tone with exercise enhances ventricular conduction and would be predicted to shorten QRS duration. Previous studies, however, have not consistently documented such changes. Using a digital electrocardiograph (ECG) cart sampling at 500 Hz, a bipolar precordial lead (V5-V2) was recorded (supine, at end expiration) in 25 healthy men (mean age 29 yr, range 19-37) at rest and immediately after submaximal treadmill exercise. QRS duration was measured on complexes recorded at high gain and expanded time scale. A significant (P less than 0.0005) decrease [4.9 +/- 2.3 (SD) ms] in QRS duration was noted, and decreased QRS duration was observed in all 25 subjects (range 1-10 ms). Furthermore there was significant (P less than 0.01) shortening of the intervals between QRS onset and Q-wave nadir (1.2 +/- 2.0 ms) and between QRS onset and R-wave peak (2.4 +/- 2.5 ms), as well as of the Q-R interval (1.3 +/- 2.7 ms). However, there were no significant differences in percent shortening of early vs. later phases of the QRS. To exclude digital sampling errors the same protocol was also applied in 11 healthy men by using an analog ECG cart. QRS duration immediately postexercise shortened by 7.1 +/- 4.3 ms (range 2-11.5 ms), which was not significantly different from the results obtained with the digital ECG. We conclude that decreased QRS duration is a physiological response to moderate treadmill exercise in healthy men, reflecting enhancement of conduction in early, middle, and later phases of ventricular activation.

Adult↗
PubMedDate not supplied

Synovial T cell receptor heterogeneity in early arthritis.

Rheumatoid arthritis (RA) has been postulated to result from a synovial immune response to an unidentified antigen(s), which should be mirrored by the T cell response. Here we investigate the T cell receptor (TCR) repertoire in the synovial tissue of patients with arthritis of early to moderate duration. We developed a nested polymerase chain reaction (PCR) technique to examine the TCR repertoire of small biopsy specimens, and show that the method is highly sensitive. We apply this technique to synovial biopsies obtained from the knee joints of patients with early to moderate duration arthritis (average duration of arthritis 1 year, range 0. 02-2.75 years). We examined biopsies from 5 normal individuals, 32 RA patients, 7 patients with seronegative spondyloarthropathy (Sp), and 12 patients with undifferentiated arthritis (UA). TCR message was detectable in 4/5 normals, 15/32 RA, 5/7 Sp, and 8/11 UA biopsies, with sampling error likely accounting for most negative biopsies. The average numbers of TCR Vbetas detected per TCR-positive biopsy were 5.0 +/- 3.7 for normals, 12.7 +/- 8.4 for RA, 18.0 +/- 7.4 for Sp patients, and 14.4 +/- 10.2 for UA. Examination of TCR messages by single-stranded conformational polymorphism analysis showed similar proportions of dominant clones in the normals compared with the patients with inflammatory arthritis. Sequence analysis was performed on 33 dominant clones from 16 patients. Sequence alignment of the third hypervariable regions showed some evidence of disease-specific sequence clustering for Sp, while some RA sequences showed similarity to previously described motifs. These data indicate greater TCR heterogeneity in early Sp and UA compared with normal synovium. Disease-specific TCR sequences may occur in early RA and Sp.

Adult↗
PubMed2001

Detection of the 67-kD laminin receptor in prostate cancer biopsies as a predictor of recurrence after radical prostatectomy.

OBJECTIVES: Reliable prognostic indicators are needed for a better pretherapeutic assessment of the agressiveness of organ-confined prostate cancer (PC) lesions. The 67-kD laminin receptor (67LR) is a cell-surface-associated protein involved in the acquisition of the invasive and metastatic phenotype of a variety of human cancer cell types. We have previously shown that 67LR detection in PC tissues from radical prostatectomy (RP) specimens is an independent predictor of biochemical (PSA) relapse in patients with clinically localized PC. In this study, we assessed 67LR detection in diagnostic PC biopsies as a predictor of biochemical relapse after RP. METHODS: Diagnostic biopsy and subsequent RP tissue specimens from 151 patients with clinically localized PC were immunohistochemically analyzed for 67LR expression. The level of 67LR expression was evaluated by both intensity and extent of the staining. Clinicopathological preoperative and postoperative parameters, including 67LR expression, were correlated with each other and tested as predictors of biochemical relapse. RESULTS: 67LR was detected in 67.5 and 68.2% of biopsies and RPs, respectively. 67LR detection in RP specimens was an independent predictor of relapse. The level of 67LR expression in the biopsy was significantly associated with the biopsy Gleason score (p<0.05) but failed to predict the pathological stage (p>0.1). Biochemical progression-free estimates for patients whose biopsy did or did not express the protein differed with only borderline statistical significance (p = 0.05). Multivariate analysis identified biopsy Gleason score as the only independent preoperative predictor of recurrence. Significant discrepancies in levels of 67LR expression were found between matched biopsy and RP specimens (p<0.05), with exact agreement rates <40%. CONCLUSIONS: 67LR detection in PC biopsies was not a significant preoperative predictor of outcome after RP. Heterogeneity of 67LR expression and biopsy sampling errors most likely represented the main reasons for discordant results between biopsy and RP specimens.

Adenocarcinoma↗
PubMedDate not supplied

Coincident Warthin's tumor and intraparotid dermatopathic lymphadenopathy. Report of a case.

A 52-year-old patient underwent excision of a parotid lump which was fond to consist of a Warthin's tumor coexistent with a lymph node involved in dermatopathic lymphadenopathy. A preoperative fine-needle aspiration specimen contained brown pigment-granule-laden macrophages within the background of many lymphocytes. Failure to correctly diagnose the parotid tumor was likely due to a sampling error.

Adenolymphoma↗
PubMed1987

[Value of rapid biopsy studies in the intraoperative assessment of axillary lymph node involvement in breast cancer].

In a prospective, randomized trial in breast-cancer patients, the surgical procedure and the adjuvant regimen were determined intraoperatively, depending on the axillary lymph node involvement. Therefore, it was necessary to perform frozen section examinations on axillary lymph nodes. In this context it was important to analyze the value of the frozen section technique of lymph nodes in predicting axillary node involvement. In 162 patients with primary breast cancer we compared the results of the frozen sections and the paraffin histology. In 96% the intraoperative diagnosis was correct and in 4% (7 cases) the results were wrong. In 6 cases we observed a sampling error and in one case a small metastasis was misinterpreted as sinus histiocytosis. In these 7 cases less than 4 lymph nodes were examined in frozen sections and the total axillary node involvement was small (less than 4 involved nodes). There was no false positive report in this series. We conclude that frozen section examinations of axillary lymph nodes are suitable for intraoperative lymph node assessment, if at least 4 of the macroscopically most suspicious lymph nodes are observed. The final histological axillary staging (number of involved lymph nodes) has to be performed on paraffin-embedded material.

Biopsy↗
PubMedDate not supplied

Cytology of lleal conduit urine in bladder cancer patients: diagnostic utility and pitfalls.

OBJECTIVE: To study the cytomorphology of urine obtained from the ileal conduit and to determine its utility and identify the pitfalls. STUDY DESIGN: Urine specimens from 469 cases of suspected or proven bladder cancer received over a period of 5 years were analyzed in the cytology laboratory. In 35 cases, total bladder resection was followed by ileal conduit reconstruction. The follow-up cytologic analysis of these 35 ileal conduit cases formed the basis of this study. RESULTS: There was absence of urothelial cells in all but 2 cases. The smear predominantly showed small, scattered intestinal mucosal cells with pyknotic nuclei, extensive karyorrhexis and numerous bacteria. In 2 cases, cytology proved superior to endoscopy and radiology in detecting recurrent disease. We had 2 false negative cases, and the negativity was attributed to sampling errors. There was 1 false positive case in which 3-dimensional clusters of intestinal columnar cells were erroneously diagnosed as adenocarcinoma. CONCLUSION: Urine obtained from ileal conduit specimens shows a smear picture that is different from that of specimens from the bladder. Thus, it is imperative to understand the difference between the cytomorphology of bladder urine and ileal conduit urine, to minimize the pitfalls and increase diagnostic utility.

Bacteria↗
PubMedDate not supplied

Cytohistologic correlation of cirrhosis and hepatocellular carcinoma. Pitfall in diagnosis?

OBJECTIVE: To compare the diagnostic criteria for cirrhosis and hepatocellular carcinoma (HCC) noted on liver fine needle aspirates (FNAs) and their corresponding liver needle core biopsies (NCBs). STUDY DESIGN: We reviewed FNA slides from 15 cases of cirrhosis and 6 cases of HCC and their corresponding NCBs. We compared a variety of specific nonarchitectural criteria, including small cell dysplasia (SCD) and large cell dysplasia (LCD), for distinguishing cirrhosis from HCC. RESULTS: FNA smears diagnostically correlated with NCBs. The cytologic criterion with the greatest correlation in predicting HCC on FNA was SCD. This was not noted in all the core biopsies, probably due to sampling error. LCD was seen more frequently in cirrhosis than HCC on both cytology and histology and therefore was not a criterion useful in establishing a diagnosis of malignancy. The remaining cytologic criteria had good correlations but did not aid in diagnosing HCC. CONCLUSION: FNA has good cytohistologic correlation with NCB for both cirrhosis and HCC. There is an association of SCD with HCC; however, LCD is not a reliable "precancerous" change as it is commonly seen in cirrhosis and HCC. Therefore, the presence of SCD on FNA should be reported and is an indication for close clinical follow-up to exclude HCC.

Adult↗
PubMedDate not supplied

Clinical value of repeat Pap smear at the time of colposcopy.

OBJECTIVE: To determine the clinical value of a repeat (second) Pap smear at the time of colposcopy in the management of patients with recent cytologic abnormalities. STUDY DESIGN: A study of paired Pap smears and their corresponding cervical biopsies during a two-year period, commencing in June 1996, was undertaken. Pap smears and cervical biopsies from 614 patients were evaluated in the Department of Pathology, Royal Darwin Hospital, Northern Territory, Australia. To maintain uniformity, the cytologic and histologic findings were assessed according to the Bethesda System. RESULTS: The original (first) Pap smears included 288 high grade and 326 low grade lesions. The second smears showed 200 high grade, 221 low grade, 167 normal and 26 unsatisfactory cases. Punch biopsies revealed 242 high grade, 300 low grade and 72 inflammatory/reactive lesions. The changes noted in the second Pap smears and in the punch biopsies in the group originally diagnosed as having high grade disease were generally less advanced. The second Pap smears and corresponding cervical punch biopsies showed more advanced changes in the group originally diagnosed as having low grade disease. Removal of part of the abnormal epithelium during the first Pap smear and the desire of the colposcopist not to damage the surface epithelium prior to performing a cervical biopsy may account for some of these findings. Sampling errors and morphological misinterpretation may explain some of the findings. CONCLUSION: In the second smears, new cases of high grade abnormality were discovered mainly in patients with low grade changes on the first smears. Therefore, a second Pap smear at the time of colposcopy is justifiable in the group with low grade changes on the first smear.

Biopsy↗
PubMedDate not supplied

Fine needle aspiration of the breast. A probabilistic approach to diagnosis of carcinoma.

OBJECTIVE: To develop a classification scheme for reporting the results of fine needle aspiration (FNA) cytology of a breast lesion according to its likelihood of being a carcinoma. STUDY DESIGN: To verify the validity of this scheme, we studied a total of 267 FNAs that were prospectively classified according to predefined criteria as positive (76), suspicious (41), proliferative with atypia (66), proliferative without atypia (48) and unremarkable (36), and compared these results with the final histology. RESULTS: The percentages of patients who had carcinoma on histology were 100% (76), 93% (38), 35% (23), 6% (3) and 31% (11) of cases diagnosed as positive, suspicious, atypical proliferative, proliferative without atypia and unremarkable on cytology, respectively. However, if only invasive carcinoma is considered, then the percentage of carcinoma was 99% (75), 93% (38), 23% (15), 2% (1) and 11% (4), respectively. The only invasive carcinoma in the proliferative-without-atypia category was a tubular carcinoma and represented a false negative diagnosis. All four invasive carcinomas with an unremarkable cytologic diagnosis were due to sampling errors. Definitive surgery after FNA was common in cases with positive (65%) and suspicious (42%) cytologic diagnosis, whereas all but one patient with atypical, proliferative and unremarkable diagnoses had a biopsy initially. CONCLUSION: This scheme of reporting breast FNA results with defined criteria according to the probability of identifying carcinoma provides a rational basis for guidelines for the management of breast lesions.

Biopsy, Needle↗
PubMedDate not supplied

Thymic neoplasia as represented by fine needle aspiration biopsy of anterior mediastinal masses. A practical approach to the differential diagnosis.

OBJECTIVE: To evaluate the cytomorphology of thymoma and to discuss the potential diagnostic pitfalls and a practical approach, which sometimes uses ancillary studies, in distinguishing various lesions of anterior mediastinal masses. STUDY DESIGN: A review of 25 fine needle aspiration (FNA) specimens of anterior mediastinal masses of thymic origin from 24 patients. RESULTS: The FNA diagnoses were thymoma in 16 aspirates, thymic/poorly differentiated carcinoma in 2, necrotic fluid/debris in 2, small lymphocytic proliferation in 2, hyperplastic thymic tissue in 1, benign cyst in 1, and scant tissue in 1. In 22 cases that had histologic confirmation, the diagnoses of 19 (86%), including 14 thymomas, concurred with the FNA diagnoses. Sampling error was responsible for the discrepancy in the remaining three cases. The cytologic evaluation of thymoma revealed a characteristic dual population of predominantly small lymphocytes and occasional large, atypical lymphocytes intimately admixed with relatively bland epithelial cells. Differential diagnoses of thymoma in the mediastinal aspirates included a variety of entities, depending on which component predominated. CONCLUSION: FNA of anterior mediastinal thymic lesions generally yields adequate cellular tissue with distinct cytologic and immunophenotypic features that enable precise classification. Caution in interpretation should be taken when the FNA yields only necrotic fluid or scanty material or when the patient is younger than the typical age range for thymoma. When the FNA diagnosis is coupled with clinical and radiographic findings, a definitive diagnosis can be generally rendered without open biopsy.

Adolescent↗
PubMedDate not supplied

Atypical squamous cells of undetermined significance. A cytohistologic study of 52 cases.

OBJECTIVE: To evaluate the significance of atypical squamous cells of undetermined significance (ASCUS) by correlating the histologic findings following a diagnosis of ASCUS on a cervical cytologic smear. STUDY DESIGN: Eighty-four smears that had been called ASCUS over a five-month period and that had corresponding histologic material were reviewed independently. Only 52 of the 84 cases on which a consensus was reached were retained for the current study. RESULTS: The breakdown of the follow-up histologic diagnoses was as follows: 28 cases (54%) were negative (without squamous intraepithelial lesions [SIL]); 22 cases (42%) showed SILs, of which 14 (27%) were low grade, 5 (10%) were high grade and 3 (5%) had SILs that could not be further classified because of fragmentation of the endocervical curettings. Finally, two cases (4%) proved to be invasive cervical carcinoma on histology despite smears that were satisfactory and not limited by the quantity or quality of material; in these the discrepancy was attributed to sampling error. CONCLUSION: Patients whose cervical cytologic smears fall into the category of ASCUS may, on follow-up, exhibit a wide spectrum of findings, ranging from no pathologic abnormality to frequent SIL and even to invasive carcinoma in rare instances. A diagnosis of ASCUS on smears warrants careful follow-up and investigation.

Carcinoma, Squamous Cell↗
PubMedDate not supplied

False positive cervicovaginal cytology. A follow-up study.

OBJECTIVE: To determine what percentage of cervical cytologic diagnoses initially classified as false positives (based on a negative cervical biopsy within three months of the cervical cytologic smear) are recategorized as histologic false negatives when subsequent studies reveal abnormalities. STUDY DESIGN: A three-year review of 1,242 cervicovaginal biopsies with corresponding cytology in the preceding three months revealed 68 cases (5.5%) where the cytology was positive for a squamous intraepithelial lesion but the biopsy was within normal limits or showed benign cellular changes. Follow-up cytologic and/or histologic diagnoses were obtained for 53 of the 68 cases from the patients' hospital and physician office records. RESULTS: Of the 53 cases with follow-up, 24 (45%) were found to have a subsequent squamous intraepithelial lesion (indicating a sampling error at the time of the initial biopsy), and 9 showed atypical squamous cells of undetermined significance. In addition, 9 of the 20 patients (45%) who had negative follow-up studies had benign abnormalities on the initial, noncorrelating biopsy that may have contributed to the discrepancy. CONCLUSION: This study emphasized the importance of diligent follow-up of patients with noncorrelating studies since they represent a population at high risk for the subsequent detection of premalignant conditions.

Biopsy↗
PubMedDate not supplied

Nongynecologic cytology utilizing the ThinPrep Processor.

OBJECTIVE: To assess the utility of the ThinPrep Processor (TP) for nongynecologic cytology. STUDY DESIGN: We reviewed the number of unsatisfactory specimens from the esophagus, common bile duct, hepatic duct, pancreas, gastric, bronchial wang, vertebra, submandibular area and neck over a one-year period, before and after TP implementation. For a one-year period after TP implementation, the cytologic diagnoses of selected TP specimens with corresponding surgical tissue diagnoses were compared, and the TP slides were reviewed in discrepant cases. RESULTS: The number of unsatisfactory specimens was reduced from 17% to 1% after TP implementations. The cytologic diagnoses of 145 TP specimens were in agreement with surgical tissue diagnoses. However, in 43 cases the cytology and tissue diagnoses were discordant. On review of 26 of the discrepant cases, the majority of TP slides were cellular, with good nuclear and cytoplasmic detail. Discrepancies resulted from sampling errors in 19 cases and TP interpretation errors in 7 cases. CONCLUSION: In our laboratory, TP is a reliable processor for nongynecologic specimens.

Cell Nucleus↗
PubMed2004

How many clusters? An information-theoretic perspective.

Clustering provides a common means of identifying structure in complex data, and there is renewed interest in clustering as a tool for the analysis of large data sets in many fields. A natural question is how many clusters are appropriate for the description of a given system. Traditional approaches to this problem are based on either a framework in which clusters of a particular shape are assumed as a model of the system or on a two-step procedure in which a clustering criterion determines the optimal assignments for a given number of clusters and a separate criterion measures the goodness of the classification to determine the number of clusters. In a statistical mechanics approach, clustering can be seen as a trade-off between energy- and entropy-like terms, with lower temperature driving the proliferation of clusters to provide a more detailed description of the data. For finite data sets, we expect that there is a limit to the meaningful structure that can be resolved and therefore a minimum temperature beyond which we will capture sampling noise. This suggests that correcting the clustering criterion for the bias that arises due to sampling errors will allow us to find a clustering solution at a temperature that is optimal in the sense that we capture maximal meaningful structure--without having to define an external criterion for the goodness or stability of the clustering. We show that in a general information-theoretic framework, the finite size of a data set determines an optimal temperature, and we introduce a method for finding the maximal number of clusters that can be resolved from the data in the hard clustering limit.

Journal Article↗
PubMed1999

Predicting epistasis from mathematical models.

Classically, epistasis is either computed exactly by Walsh coefficients or estimated by sampling. Exact computation is usually of theoretical interest since the computation typically grows exponentially with the number of bits in the domain. Given an evaluation function, epistasis also can be estimated by sampling. However this approach gives us little insight into the origin of the epistasis and is prone to sampling error. This paper presents theorems establishing the bounds of epistasis for problems that can be stated as mathematical expressions. This leads to substantial computational savings for bounding the difficulty of a problem. Furthermore, working with these theorems in a mathematical context, one can gain insight into the mathematical origins of epistasis and how a problem's epistasis might be reduced. We present several new measures for epistasis and give empirical evidence and examples to demonstrate the application of the theorems. In particular, we show that some functions display "parity" such that by picking a well-defined representation, all Walsh coefficients of either odd or even index become zero, thereby reducing the nonlinearity of the function.

Algorithms↗
PubMed2000

Olfactory mucosal findings in patients with persistent anosmia after endoscopic sinus surgery.

Sixty-three biopsy specimens were obtained from the olfactory region of 15 patients with persistent anosmia and 6 patients with normosmia after sinus surgery. Immunohistochemical examination of all specimens with microtubule-associated protein 5 (MAP5) antisera demonstrated olfactory epithelium in 11 of 18 specimens from normosmic patients and in 12 of 45 samples from anosmic patients. There was a significant difference in the proportion of specimens containing olfactory epithelium between the two groups of patients. In normosmic patients, most of the biopsy samples contained normal-appearing olfactory tissue. However, 2 main patterns of histologic findings were noted in the olfactory mucosa of anosmic patients. First, the olfactory receptor cells were remarkably decreased in number. Second, the orderly arrangement of cells characteristic of normal olfactory epithelium was lost, demonstrating a degenerative appearance. These data suggest that olfactory epithelium can be degenerated even in chronic sinusitis and thereafter extensively replaced with respiratory epithelium, resulting in increased sampling error. Moreover, an unimproved olfactory deficit after sinus surgery may be due to the abnormalities observed at the olfactory epithelium level.

Adolescent↗
PubMed2002

An example of maximizing survey return rates. Methodological issues for health professionals.

Obtaining a high response rate in survey research can bolster statistical power, reduce sampling error, and enhance the generalizability of the results to the population surveyed. We describe a mail survey designed to achieve a high return rate of completed questionnaires from members of the American Psychological Association who were engaged in clinical practice. We adapted the Total Design Method for survey research and were able to achieve a high response rate (68%) among health professionals. This was not an experiment in which we assessed the best method to increase survey response rates, hence we cannot empirically evaluate how each of the steps influenced our overall response rate. Future research is needed to identify the relative effectiveness of each of these principles in enhancing survey response rates. Research is also needed to distinguish general principles that apply across populations from those that must be tailored to specific subpopulations.

Child↗
PubMedDate not supplied

Expected value of sample information calculations in medical decision modeling.

There has been an increasing interest in using expected value of information (EVI) theory in medical decision making, to identify the need for further research to reduce uncertainty in decision and as a tool for sensitivity analysis. Expected value of sample information (EVSI) has been proposed for determination of optimum sample size and allocation rates in randomized clinical trials. This article derives simple Monte Carlo, or nested Monte Carlo, methods that extend the use of EVSI calculations to medical decision applications with multiple sources of uncertainty, with particular attention to the form in which epidemiological data and research findings are structured. In particular, information on key decision parameters such as treatment efficacy are invariably available on measures of relative efficacy such as risk differences or odds ratios, but not on model parameters themselves. In addition, estimates of model parameters and of relative effect measures in the literature may be heterogeneous, reflecting additional sources of variation besides statistical sampling error. The authors describe Monte Carlo procedures for calculating EVSI for probability, rate, or continuous variable parameters in multi parameter decision models and approximate methods for relative measures such as risk differences, odds ratios, risk ratios, and hazard ratios. Where prior evidence is based on a random effects meta-analysis, the authors describe different ESVI calculations, one relevant for decisions concerning a specific patient group and the other for decisions concerning the entire population of patient groups. They also consider EVSI methods for new studies intended to update information on both baseline treatment efficacy and the relative efficacy of 2 treatments. Although there are restrictions regarding models with prior correlation between parameters, these methods can be applied to the majority of probabilistic decision models. Illustrative worked examples of EVSI calculations are given in an appendix.

Algorithms↗