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PubMed1999

Context effects in lexical access: a meta-analysis.

The modularity hypothesis was evaluated in this review of 25 studies that investigated context effects in early lexical processing. Selection criteria restricted the review to priming studies and to studies that presented the target word before or at the end of the prime word. Meta-analysis was used to provide summary information about the 17 studies in the review for which effect sizes could be calculated. Overall, the analysis revealed a small effect of context on lexical access. Results provide a disconfirmation of the modularity hypothesis; although multiple interpretations of a word were sometimes accessed, the contextually appropriate interpretation was consistently more strongly activated. The lack of significant heterogeneity of variance suggests that the variability observed across studies was due to sampling error; however, task, timing of target presentation, meaning frequency, type of target, and type of context were identified as potential moderator variables.

Humans↗
PubMed1999

The rate of homozygous CDKN2A/p16 deletions in glioma cell lines and in primary tumors.

The rate of homozygous deletions of CDKN2A/p16 is variable between different tumor entities, and in addition it is higher in established cell lines in comparison with primary tumors. Such incongruencies may reflect statistical sampling errors, true differences depending on tissue derivatisation and CDKN2A/p16 loss under selective pressure in tissue culture. Clarification of these issues is warranted in the context of defining tumor suppressor genes such as CDKN2A/p16 as targets for gene replacement therapies. We therefore compared established cell lines derived from human glioblastomas and their corresponding primary tumors by multiplex PCR methodology. Archival early passages were included to determine the time point at which the p16 status of a cell line changes if it is different from the original tumor. It was found that in 2 of 11 cases (18%) the primary tumor had no p16 alteration whereas the corresponding cell lines had a homozygous p16 deletion. Tracking the in vitro evolution of these two cell lines we found that CDKN2A/p16 was lost already in the earliest passages. This suggests a clonal outgrowth advantage of a subpopulation of p16 deleted tumor cells rather than instability of the CDKN2A/p16 genotype in vitro. Including 20 additional glioblastoma-derived cell lines we detected that in 19 of the total 31 lines at least one exon was lost bringing the rate of p16 loss in the whole panel to 61%. This compares to a rate of 49% which was found in original glioma tissue from 47 unselected other patients. It is concluded, that in cell culture selective pressure favours the outgrowth of pre-existing CDKN2A/p16 negative clones, which account for the difference of CDKN2A/p16 status between cell lines and tumors. In no case did we see a change of the CDKN2A/p16 status during prolonged tissue culture periods of up to 8 years.

Adult↗
PubMed1998

Ludwig Symposium on biliary disorders--part II. Pathologic features and evolution of primary biliary cirrhosis and primary sclerosing cholangitis.

Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) share many clinical and pathologic features. Central to the symptoms and biochemical alterations of both conditions is a substantial loss of intrahepatic bile ducts, leading to interference with bile flow. This pathologic change may ultimately result in cirrhosis of the biliary type. In addition, however, biopsy specimens usually show an element of liver-cell destruction and associated inflammation, mainly interface hepatitis. This finding is more pronounced in PBC than in PSC but can lead in both diseases to features that resemble those of cirrhosis as a result of hepatitis virus infection. The resemblance often leads to diagnostic confusion, which is easily overcome by attention to the clinical, radiologic, serologic, and biochemical context. Histologic staging of PBC and PSC has led to a greater appreciation of their evolution but is hampered in biopsy material by sampling error. Examination of explanted livers at transplantation has demonstrated a wide variation in the maturation of lesions in various parts of the organ.

Biopsy, Needle↗
PubMed2000

Analysis of false-negative diagnoses on endoscopic brush cytology of biliary and pancreatic duct strictures: the experience at 2 university hospitals.

CONTEXT: Endoscopic brush cytology is a valuable technique for the diagnosis of pancreatobiliary malignancy. Despite its widespread use, the sensitivity of this method has been reported as approximately 50%. The specificity is usually higher than 95%. Few reports have systematically analyzed the reasons for this relatively low sensitivity. OBJECTIVES: To determine the rate and reasons for false-negative diagnoses in endoscopic brushing cytology of biliary and pancreatic ducts based on the results of sensitivity, specificity, accuracy, and positive and negative predictive values. DESIGN: Retrospective analysis of laboratory data and slide review of false-negative cases. SETTING: Two tertiary care state university hospitals. PATIENTS: A total of 183 pancreatobiliary brushing specimens obtained from patients undergoing endoscopic retrograde cholangiopancreatography for biliary or pancreatic duct disease for a 4- to 5-year period. INTERVENTION: Endoscopic retrograde cholangiopancreatography brushings. MAIN OUTCOME MEASURES: Determination of sensitivity, specificity, accuracy, and positive and negative predictive values. Analysis of false-negative results. RESULTS: The sensitivity, specificity, accuracy, and positive and negative predictive values, overall, were 48%, 98%, 79%, 92%, and 76%, respectively. Sampling error was a major cause of false-negative diagnoses (67%), followed by interpretive (17%) and technical errors (17%). CONCLUSIONS: Improvements in sensitivity and diagnostic accuracy for cancer of the pancreatobiliary tract can be achieved by optimizing slide preparatory techniques. Also, enhancement of the cytologist's diagnostic skills enables the identification of the morphologic features of premalignant lesions. Repeat brushings are indicated for suspicious or negative results not consistent with the clinical or radiologic findings.

Bile Duct Diseases↗
PubMed2005

Frozen section diagnosis in pediatric surgical pathology: a decade's experience in a children's hospital.

CONTEXT: Intraoperative consultations, including frozen sections (FSs), are essential for patient care and are a key quality component in anatomic pathology. Little data exists about the use, frequency, and type of discrepancies and deferral rates of FS diagnoses in pediatric and adolescent surgical pathology. OBJECTIVE: The purpose of this study was to analyze indications, discrepancies, and deferrals for all FSs performed at a children's hospital during a 10-year period. DESIGN: All FSs for 1995-2004 were reviewed for indications, discrepancies, deferred diagnoses, and turnaround time. Discrepancies were categorized into major and minor subtypes according to potential impact on patient care. RESULTS: A total of 35,611 surgical pathology cases were accessioned, with 2839 intraoperative consultations, which included 2783 FSs and 56 nonmicroscopic consultations. Most frequent indications included questions related to neoplasms (tumor detection, specimen adequacy, triage, classification, and margins) and suspected Hirschsprung disease. In these consultations, 115 discrepancies (4%) were identified, of which 7 (0.2%) were major, with potentially significant clinical impact, and 108 (3.9%) were minor. The major discrepancies included tumor, ganglion cell, or organism detection. The minor discrepancies involved sampling error, reclassification of benign or malignant neoplasms without clinical consequences, tumor typing or grading, and ganglion cell identification without clinical impact. Deferrals in 718 FSs (25% deferral rate) included tumor classification from generic to specific, identification of organisms, and evaluation of lymph node biopsies for lymphoma. Turnaround time exceeded 20 minutes in 403 cases (14%). CONCLUSIONS: The FS rate of 7.8% overall and 5% of surgical pathology cases is similar in children's and general hospitals. The major discrepancy (discordance) rate is lower, which may reflect the different indications for FS in children and adolescents. Evaluation of colonic biopsies for ganglion cells is a diagnostic pitfall. The deferral rate of 25% reflects the definition of a deferred diagnosis. Traditional definitions of deferred and discordant FS diagnoses should be refined to reflect the increasing use of adjunct techniques, especially in tumor classification. These findings emphasize that, in children and adolescents, most FSs are performed for tumor classification, triage, detection, and specimen adequacy, and for possible Hirschsprung disease. In children and adolescents, FSs are used infrequently to identify normal or unknown tissue, to analyze a lesion in a radiographically directed specimen, or to detect lymph node metastases. The differences in pediatric and adolescent FS indications and use underscore the importance of focused education in pediatric surgical pathology.

Frozen Sections↗
PubMed1999

MIRD pamphlet no. 16: Techniques for quantitative radiopharmaceutical biodistribution data acquisition and analysis for use in human radiation dose estimates.

This report describes recommended techniques for radiopharmaceutical biodistribution data acquisition and analysis in human subjects to estimate radiation absorbed dose using the Medical Internal Radiation Dose (MIRD) schema. The document has been prepared in a format to address two audiences: individuals with a primary interest in designing clinical trials who are not experts in dosimetry and individuals with extensive experience with dosimetry-based protocols and calculational methodology. For the first group, the general concepts involved in biodistribution data acquisition are presented, with guidance provided for the number of measurements (data points) required. For those with expertise in dosimetry, highlighted sections, examples and appendices have been included to provide calculational details, as well as references, for the techniques involved. This document is intended also to serve as a guide for the investigator in choosing the appropriate methodologies when acquiring and preparing product data for review by national regulatory agencies. The emphasis is on planar imaging techniques commonly available in most nuclear medicine departments and laboratories. The measurement of the biodistribution of radiopharmaceuticals is an important aspect in calculating absorbed dose from internally deposited radionuclides. Three phases are presented: data collection, data analysis and data processing. In the first phase, data collection, the identification of source regions, the determination of their appropriate temporal sampling and the acquisition of data are discussed. In the second phase, quantitative measurement techniques involving imaging by planar scintillation camera, SPECT and PET for the calculation of activity in source regions as a function of time are discussed. In addition, nonimaging measurement techniques, including external radiation monitoring, tissue-sample counting (blood and biopsy) and excreta counting are also considered. The third phase, data processing, involves curve-fitting techniques to integrate the source time-activity curves (determining the area under these curves). For some applications, compartmental modeling procedures may be used. Last, appendices are included that provide a table of symbols and definitions, a checklist for study protocol design, example formats for quantitative imaging protocols, temporal sampling error analysis techniques and selected calculational examples. The utilization of the presented approach should aid in the standardization of protocol design for collecting kinetic data and in the calculation of absorbed dose estimates.

Humans↗
PubMed1998

[Diagnostic examination for causes of exudative pleurisy].

In two patients, men aged 65 and 57 years with complaints of exertional dyspnoea, dry cough, diminished appetite and weight loss, the cause of pleural fluid formation was not discovered despite several diagnostic procedures. In the first patient a diffuse mesothelioma was found at autopsy. The second patient had pleurisy secondary to an adenocarcinoma in the upper lobe of the right lung; he died from lung embolism after the second, diagnostic, thoracoscopy. It can be difficult to establish the diagnosis in patients with a pleural effusion. Specific reasons for this are abundant formation of connective tissue in cases of malignant pleural disease and subsequent risks of sampling errors.

Adenocarcinoma↗
PubMed1999

[The 13C-urea breath test efficacy in determining Helicobacter pylori eradication].

Helicobacter pylori eradication therapy is useful and requires more precise determination of actual eradication. Patients often become positive for Helicobacter pylori again after presumed eradication. Reinfection is thought rare and patients with positive reconversion may be false-negative at determination. After a year, positive reconversion was 26.8% in our work after determination by culture and histopathological methods and 4.3% after these were combined with urea breath test (UBT). The positive reconversion rate is significantly lower after combination with UBT, suggesting the usefulness of UBT in determining Helicobacter pylori eradication. This may be because UBT includes no biopsy, eliminating sampling error, and highly sensitive UBT detects traces of Helicobacter pylori. The UBT is thus expected to become widely used to determine Helicobacter pylori eradication.

Breath Tests↗
PubMed1998

Diagnosis of Helicobacter pylori infection: non-invasive diagnostic tests.

The non-invasive urea breath test can demonstrate the presence of Helicobacter pylori infection with the same accuracy as invasive methods (histology, rapid urease test, culture), but with less distress and inconvenience to the patient. It is evident that this test can and should substitute invasive methods in patients with uncomplicated duodenal ulcer, in those with non-ulcer dyspepsia and in all who have gastrointestinal disorders that do not require endoscopic examination. The urea breath test has a primary role for determining the success of eradication therapy. It is ideal for short- and long-term follow-up, particularly in the case of duodenal ulcer, which is strictly related to the presence of Helicobacter pylori. In serious disease, when endoscopic examination is mandatory, such as complicated ulcer or mucose associated lymphoid tissue lymphoma, the urea breath test can still improve the diagnostic accuracy of Helicobacter pylori infection as it does not imply sampling error, to which biopsy is subject.

Biopsy↗
PubMed1998

Atrophy, metaplasia and dysplasia: are they reversible?

The eradication of Helicobacter pylori results in the decrease and eventual disappearance of inflammation in the gastric mucosa. An important question with practical implications is whether treatment of H. pylori can promote the resolution of atrophy and intestinal metaplasia. If this happens, then one could infer that even in the presence of established multifocal atrophic gastritis the cure of Helicobacter pylori could reduce the risk of developing gastric cancer. Several investigators have addressed the issue, but the cumulative results remain inconclusive. The great latitude that there exists in the interpretation of the concept of atrophy and the patchy distribution of both atrophic changes and intestinal metaplasia (with resulting inevitable sampling error) are important reasons for the wide discrepancy in the conclusions reached by different authors. Controlled, long-term prospective studies conducted in different ethnic and geographic settings are needed to provide sound evidence-based answers to the question of reversibility of atrophy, intestinal metaplasia, and epithelial dysplasia.

Atrophy↗
PubMed1996

Diagnosis of Helicobacter pylori infection.

A number of reliable methods are currently available for the diagnosis of Helicobacter pylori infection. These diagnostic tests can be classified into invasive methods that require endoscopy and gastric biopsy, and noninvasive methods. Invasive methods include gastric mucosal biopsies at endoscopy for bacteriologic culture, histology, and the rapid urease test. Noninvasive methods include the urea breath test and serologic tests. Each of these diagnostic tests has its advantages and disadvantages. Histologic examination remains the gold standard for diagnosis. It can also detect coccoidal forms of the bacteria and be used to assess the severity of gastritis. Culture of H pylori should be performed if antibiotic sensitivity of the organism is required. A rapid urease test is the quickest test for H pylori status. The urea breath test detects urease activity in the entire stomach, thus eliminating the possibility of a sampling error, which occurs in random gastric biopsies. Serologic tests using either ELISA or latex-agglutination methods are excellent for diagnosis of H pylori infection, but not useful for monitoring effects of therapy. Recently, the polymerase chain reaction has been applied to fixed-tissue biopsies, as well as body secretions in the diagnosis of H pylori infection.

Biopsy↗
PubMed1976

Ultrastructural and physiological changes induced by atractylate in the canine myocardium.

The myocardial cellular response to the cardiac glycoside atractylate, a known inhibitor of mitochondrial adenine nucleotide translocation, was examined physiologically, morphologically, and morphometrically in eight dogs. An isolated in situ segment of left ventricular tissue was employed in these experiments to eliminate collateral flow and the potential for large sampling error. It was found that atractylate infusion rapidly induced physiological and morphological changes suggestive of a loss of membrane regulation of ion flux in the arteriole, capillary endothelium, and myocardial cell. Also mitochondrial changes suggestive of adenine nucleotide translocase inhibition were observed. As these responses are similar to those induced by acute myocardial ischaemia, it is suggested that ischaemia and atractylate induce cell injury by similar mechanisms.

Animals↗
PubMed1999

Pathologic examination of sentinel lymph nodes in breast cancer.

Lymphatic mapping with selective sentinel lymphadenectomy allows accurate pathologic examination of the nodes most likely to contain macro- or micrometastastic disease for staging and proper adjuvant chemotherapy. The hypothesis of SLN biopsies was histopathologically validated by Turner et al that if the node is tumor free by H&E and immunohistochemistry, the probability of non-SLN involvement is less than 0.1%. Giuliano et al and Veronesi et al reported that detection of metastases in SLNs by frozen section technique is 89% and 64%, respectively. At MCC, frozen section evaluation of SLN is not performed because of its potential loss of micrometastasis in the cryostat, freezing artifacts, sampling error, and perhaps radioactive contamination. Intraoperative detection of macro- or micrometastasis is critical because it enables conversion of patients with positive SLN to CLND in one surgical setting more cost-effectively. IIC of the lymph nodes has been used routinely in the diagnosis of hematologic malignancies and also in breast cancer as a useful method in many series. In the author's experience, IIC by Diff-Quik stain converted 100% of grossly positive and suspicious SLNs and 22% of grossly negative SLNs. The significance of detecting micrometastases in axillary lymph nodes using immunohistochemical techniques has been reported in many series. At the MCC, routine use of CKI on paraffin sections of grossly negative SLNs enabled the upstaging of 10.6% of patients from N0 to N1. Recent addition of intraoperative rapid CKI as an adjunct to complement Diff-Quik stain has proven to be more sensitive in detecting micrometastases than using Diff-Quik stain alone. IIC technique using either Diff-Quik stain or CKI requires intensive training and experience to avoid potential pitfalls and errors in interpretation. Evaluation of SLN should use methods that enhance the ability to detect micrometastasis, however, in a cost-effective manner. The cost-effectiveness of IIC by Diff-Quik stain is incomparable with frozen section evaluation. The added cost of routine immunohistochemical stain and perhaps multiple levels of H&E stain should be offset by the decreased costs of IIC and clinically by treating most patients in the outpatient settings. In summary, IIC by Diff-Quik stain is simple, rapid, and has excellent diagnostic accuracy in grossly positive and suspicious SLNs allowing cost-effective, immediate CLND. IIC by CKI is an extremely useful ancillary technique that complements Diff-Quik stain in detecting micrometastases particularly in low grade ductal or lobular carcinoma and low tumor cell volume. Appropriate combined use of both stains may lead to intraoperative nodal staging and cost-effective CLND. SLN mapping technology at MCC using IIC in conjunction with serial sections, entire tissue submission, routine use of CKI, and multiple levels of the SLN have led us to uncover micrometastasis in high-risk, traditionally node-negative patients. These results have encouraged investigators to pursue even more sensitive techniques to detect micrometastases, including molecular biology techniques such as RT-PCR. Experienced cytopathologists and active cytopathology services are required to avoid potential pitfalls in performing and interpreting IIC. More long-term follow-up and prospective trials are needed to determine the prognostic significance of upstaging by ancillary techniques, which may lead to a revision of the current TNM staging system.

Axilla↗
PubMed1999

Regional reproducibility of microsatellite instability in sporadic colorectal cancer.

The reproducibility of microsatellite instability from different regions of the same sporadic colon cancer has not been addressed. We therefore microdissected and extracted DNA from three to nine separate regions of 13 highly unstable sporadic colon cancers. Each region was then evaluated by polymerase chain reaction amplification of 17 microsatellites: 10 tetranucleotide repeats, 2 noncoding mononucleotide repeats (BAT-26 and BAT-40), and 5 coding mononucleotide repeats (TGFBRII, BAX, MSH3, MSH6, IGFIIR). Microsatellite instability showed 100% regional reproducibility with respect to either the panel of 10 tetranucleotide repeats or BAT-26, and nearly 100% reproducibility with BAT-40, although regional variation in the percent instability and the size of unstable alleles was present. TGFBRII was more frequently mutated than any other coding mononucleotide repeat; frame shifts in this gene were identified in nearly every region of every tumor. Each of the five coding repeats showed regional variability in at least one tumor, and 10 of the 13 tumors showed variability with at least one coding repeat. This variability took the form of different mutant alleles (TGFBRII, BAX, MSH3) or mutations present in some but not all regions of a tumor (MSH6, IGFIIR, BAX, MSH3). We conclude that the regional reproducibility of generalized microsatellite instability as measured by noncoding repeats indicates that sampling is not a problem in these highly unstable tumors, and that the mismatch repair deficiency phenotype is acquired in the very late adenoma stage or early cancer stage of sporadic colonic tumorigenesis. The high frequency of TGFBRII mutations is consistent with acquisition of these mutations at a similar stage of tumorigenesis. The regional variability with respect to the presence or absence of a mutation in the other four coding mononucleotide repeats could lead to sampling error and is consistent with a somewhat later time of acquisition of these mutations. Genes Chromosomes Cancer 26:106-114, 1999.

Adult↗
PubMed1999

The diagnosis and management of Barrett's esophagus.

Since its description in the 1950s, the definition of Barrett's esophagus has evolved from the macroscopic visualization of gastric-appearing mucosa in the esophagus to the histologic identification of goblet cells confirming the presence of intestinal metaplasia within the esophagus. The length of intestinal metaplasia necessary to be classified as Barrett's, and the relationship between intestinal metaplasia of the esophagus and that limited to the cardia are all areas currently being evaluated. However, any segment of intestinal metaplasia is capable of undergoing dysplastic change and ultimately of becoming a focus of adenocarcinoma. It is logical to expect the degree of risk for developing cancer to be proportional to the amount of intestinal metaplasia present; however, within a population, the low risk to any individual is balanced by the relative frequency of the process. Thus, given the large numbers of people in America with CIM, even a small risk of progression to cancer will result in a large number of patients with adenocarcinoma of the cardia. This is exactly what is occurring today, with the incidence of adenocarcinoma of the cardia and esophagus currently rising faster than any other cancer in the United States. A major risk factor for adenocarcinoma of the esophagus is intestinal metaplasia, which occurs as a consequence of GERD. Patients with Barrett's esophagus usually have more severe reflux disease with significant impairment of LES function and esophageal body motility compared with patients without Barrett's. Furthermore, in patients with Barrett's, the composition of the refluxed juice is different. Patients who reflux both gastric and duodenal juice have a higher prevalence of Barrett's than do those who reflux gastric juice alone. Among patients with Barrett's, a significantly greater esophageal bilirubin exposure has been demonstrated in those with dysplasia. The mechanically defective sphincter and impaired esophageal body function in many patients with Barrett's makes their disease difficult to control medically. In addition, symptoms are unreliable as a guide to successful control of reflux. The hardest symptom to control is regurgitation, and there is concern that this and continued reflux of pharmacologically altered gastric contents, particularly bile acids in their nonpolar form, may contribute to progression of Barrett's. Both medical therapy and failed antireflux surgery are associated with progression of Barrett's to dysplasia and adenocarcinoma. On the other hand, a functioning fundoplication seems to be associated with protection from progression of Barrett's. Intestinal metaplasia of the esophagus is unlikely to regress after antireflux surgery; however, intestinal metaplasia limited to the cardia is perhaps more dynamic and able to regress. Furthermore, low-grade dysplasia frequently regresses after an antireflux procedure. Antireflux surgery is safe, effective, and durable, and often can be performed using minimally invasive techniques. Thus, antireflux surgery should be strongly considered in any patient with intestinal metaplasia of the esophagus or cardia. The possibility of mucosal ablation after an antireflux repair should be considered in patients with low-grade dysplasia. Patients with Barrett's and high-grade dysplasia are at high risk for having a focus of adenocarcinoma present. Even with multiple biopsies, a degree of sampling error exists. Also, adenocarcinoma can develop within the space of several months; and if the cancer is allowed to invade into the submucosa, 50% of these patients will have lymphatic metastases, thereby negating the purpose of surveillance. Although patients with high-grade dysplasia and intramucosal adenocarcinoma on biopsy who do not have an endoscopically visible lesion are unlikely to have lymphatic metastases, 7% do have submucosal invasion. Thus, even in these very early tumors, treatment directed only at the mucosa may be inadequate. (ABSTRACT

Adenocarcinoma↗
PubMed1999

Influence of lactation on the prolactin secreting cells of the hypophysis of impala (Aepyceros melampus): an immunocytochemical and computer image analysis study.

Acute stress in the course of wildlife management has been intensively investigated. Chronic stress, on the contrary, has not been researched at all, probably due to the difficulty in measuring it as a result of the overriding effect of the physiological response to the restraining of wild animals. It was therefore decided to evaluate the use of immunocytochemistry, combined with computer image analysis to try and determine the magnitude of the structural changes of various hormone-secreting cells of the hypophysis. Since it was a pilot study to determine whether the combination of immunocytochemistry with computer image analysis could be of value to distinguish between two normally diverse groups, it was decided to compare the relative activity of prolactin secreting cells of lactating and non-lactating impala ewes. After transforming the prolactin immunoreactive area data by log10 to fall inside the parameters for kurtosis and skewness, a significant difference (P < 0.05, 5-% level, 2-tail) with the parametric t-test could be shown between the mean prolactin immunoreactive area of lactating (3.0751 micron 2) and non-lactating (3.0467 micron 2) ewes. However, the Pearson product moment (r = 0.03) showed that this difference may not be important for all practical reasons. This may be due to either sampling errors or limitations of computer image analysis, as it was often difficult to distinguish individual prolactin immunoreactive areas. Furthermore, a significant increase in the total prolactin immunoreactive areas of lactating ewes was also established. This technique, however, could distinguish between the hypophysis of lactating and non-lactating impala ewes, and with further refinement could be a useful tool in determining chronic stress in wildlife populations.

Animals↗
PubMed2000

Relative distribution of synapses in the A-laminae of the lateral geniculate nucleus of the cat.

Previous electron microscopic studies of synaptic terminal distributions in the lateral geniculate nucleus have been flawed by potential sampling biases favoring larger synapses. We have thus re-investigated this in the geniculate A-laminae of the cat with an algorithm to correct this sampling bias. We used serial reconstructions with the electron microscope to determine the size of each terminal and synaptic type. We observed that RL (retinal) terminals are largest, F (local, GABAergic, inhibitory) terminals are intermediate in size, and RS (cortical and brainstem) terminals are smallest. We also found that synapses from RL terminals are largest, and thus most oversampled, and we used synaptic size data to correct for sampling errors. Doing so, we found that the relative synaptic percentages overall are 11.7% for RL terminals, 27.5% for F, and 60.8% for RS. Furthermore, we distinguished between relay cells and interneurons with post-embedding immunocytochemistry for GABA (relay cells are GABA negative and interneurons are GABA positive). Onto relay cells, RL terminals contributed 7.1%, F terminals contributed 30.9%, and RS terminals contributed 62.0%. Onto interneurons, RL terminals contributed 48.7%, F terminals contributed 24.4%, and RS terminals contributed 26.9%. We also found that RL terminals included many more separate synaptic contact zones (9.1 +/- 1.6) than did F terminals (2.6 +/- 0.2) or RS terminals (1.02 +/- 0.02). We used these data plus the calculation of overall percentages of each synaptic type to compute the relative percentage of each terminal type in the neuropil: RL terminals represent 1.8%, F terminals represent 14.5%, and RS terminals represent 83.7%. We argue that this relative synaptic paucity is typical for driver inputs (from retina), whereas modulator inputs (all others) require many more synapses to achieve their function.

Algorithms↗
PubMed2000

Fine-needle aspiration cytology of bone: accuracy and pitfalls of cytodiagnosis.

BACKGROUND: Fine-needle aspiration cytology has proved to be an accurate, cost-effective, and safe technique for diagnosing inflammatory and neoplastic lesions at different body sites. Its applicability in bone pathology, however, has been controversial due to a high percentage of inadequate samples and nonspecific results in the diagnosis of primary bone lesions. In this study, the diagnostic accuracy of the technique and its capacity for diagnosing primary bone lesions were assessed. In addition, the authors analyzed the diagnostic limitations with focus on specimen adequacy. METHODS: The authors reviewed 314 consecutive fine-needle aspirations of bone from 308 patients. Direct or cytospin smears from aspirated material were fixed in 95% alcohol and stained by a modified Papanicolaou technique. Ninety-seven smears (31%) initially were considered unsatisfactory and excluded from the study. A diagnosis was rendered in 217 cases (69%), which were classified into 4 categories: primary bone lesions (benign and malignant) (42%), metastatic bone tumors (37%), suspicious for malignancy (5%), and negative (16%). RESULTS: The overall accuracy was 95%. Seventy-eight percent of primary bone lesions were correctly diagnosed by cytology. All cases diagnosed as metastatic by cytology were correct. The authors encountered difficulties diagnosing fibro-osseous lesions. Thirteen percent of cases were erroneously diagnosed as "negative" or "inflammatory conditions." On review, the absence of adequate cytologic material was noted in all of them. This sampling error could have been avoided by the presence of an on-site cytopathologist. CONCLUSIONS: Fine-needle aspiration of bone is a simple, reliable, and accurate diagnostic technique that can facilitate patient management and preoperative decision-making and/or avoid unnecessary invasive procedures for patients with primary or metastatic bone lesions. However, the radiologist, cytopathologist, and orthopedic surgeon should work together for optimal results. Moreover, a definitive pathologic diagnosis should not be issued if diagnostic material is not adequate and/or clinicoradiologic information is incompatible.

Biopsy, Needle↗