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Negative predictive value of pulmonary fine needle aspiration cytology.

Percutaneous fine needle aspiration (FNA) for cytologic examination is an accepted and reliable technique for diagnosing neoplasia. It is less useful, however, in excluding that diagnosis. We performed a retrospective analysis of a consecutive series of pulmonary FNA specimens at Memorial Sloan-Kettering Cancer Center to determine the negative predictive value (NPV) of this technique in the setting of a large cancer hospital. Fifty-seven cases were studied. Six cases (10.5%) were initially diagnosed as negative but acellular and were not further analyzed, and another 6 were lost to follow-up; 24 cases (42.1%) were subsequently confirmed negative by tissue or clinical follow-up, and 21 of the cases (36.8%) were proven positive for malignancy by repeat aspiration, tissue diagnosis or clinical means. Of these 21 cases, 1 was misdiagnosed as negative, and review demonstrated malignant cells on the slide; 3 of the 21 cases should have been initially rejected as unsatisfactory, and 18 of the 21 contained material sufficient for a cytologic diagnosis but not representative of the lesion. On follow-up the false-negative cases showed primary adenocarcinoma, epidermoid carcinoma, lymphoma, metastatic breast carcinoma and metastatic sarcoma. Specific benign diagnoses were made on the initial cytologic preparation in three cases. No benign tumors were found. The NPV in our series was 53.3%, comparable to values in previous reports. The single largest factor contributing to false-negative diagnoses is sampling error, and we recommend repeat aspiration when no specific benign diagnosis is made. In addition, we suggest that the diagnoses of negative for malignant cells and insufficient for diagnosis or acellular be considered separate categories.

Adult↗

Screening for acute myocarditis--is scintigraphy with (99m)Tc-Anti-Granulocyte BW 250/183 an answer?

BACKGROUND: Myocarditis is most often caused by Coxackie B virus, influenza viruses, and echoviruses. It is usually self-restricting and ending in full recovery, but in some patients the infection leads to congestive cardiomyopathy. It is difficult to identify patients with myocarditis using clinical criteria, laboratory tests, ECG and ultrasonography, and currently a myocardial biopsy is required to establish the diagnosis. The risk of complications, sampling error and costs of this procedure underline the need of non-invasive but sensitive methods of imaging. Several radiopharmaceuticals have been used so far to confirm inflammation: 67Ga, (99m)Tc-nanocolloids and 111In-leucocytes. Scintigraphy with radiolabeled autologous white blood cells (WBCs) is considered a very useful method in identifying sources of inflammation but is difficult to perform and time-consuming. AIMS: The aim of our study was to investigate whether scintigraphy with (99m)Tc-Anti-Granulocyte BW 250/183 antibody is a valuable diagnostic method in evaluating focal and diffuse inflammation of the heart and could therefore be suggested for use in screening for acute myocarditis. MATERIAL AND METHODS: A two dimensional scintigraphy and SPECT mode of heart imaging with the use of (99m)Tc-Anti-Granulocyte antibody (740 MBq) was performed on 14 subjects (11 males and 3 females) aged 25-60 years with a positive myocardial biopsy confirming an inflammatory process in the myocardium. After i.v. administration of the tracer a 1 minute series of planar scans was performed within the first 60 minutes. Delayed static scans were performed at 1, 2, 4 and 24 hours. RESULTS: The scintigraphic scans revealed the uptake of the tracer in the heart area in 13 patients, confirming active inflammatory process. Follow-up scintigraphy was performed 3-5 months after the first study, when the control myocardial biopsy was negative. The results of the study showed the concordance between myocardial biopsy and scintigraphy results in patients with an inflammatory process in the heart. CONCLUSIONS: Scintigraphy with the use of (99m)Tc-Anti-Granulocyte seems to be a useful diagnostic method in evaluating patients with suspected myocarditis, but further studies are needed to establish its sensitivity and specificity.

Acute Disease↗

Hepatobiliary practical: how to get the best out of a liver biopsy.

The liver biopsy has a unique place in the investigation of liver disease because the concepts and classification of liver disease are rooted in morphology. Today, the use of the liver biopsy has extended beyond that of diagnosis, to the assessment of disease progression, response to therapy and transplant rejection. To get the best out of the liver biopsy, it is necessary to appreciate the usefulness and limitations of the biopsy specimen. Aspects to consider include: (1) minimizing sampling errors, and appreciating that the changes in the biopsy may not be representative of the primary pathology, (2) good laboratory quality practices to avoid processing artifacts, which may render a biopsy undiagnosable, (3) the appropriate use of special stains and other laboratory techniques, (4) adoption of a systematic and algorithmic approach in the microscopic examination of the biopsy, and (5) good clinicopathological correlation.

Biopsy↗

[Reversibility of advanced liver fibrosis--therapeutic possibility and biochemical monitoring of the disease].

The advanced liver fibrosis and cirrhosis had been regarded irreversible until quite lately. However, experimental and clinical studies confirmed possibility of stopping or even decreasing the stage of liver fibrosis through causal factor elimination and application of pharmacological preparation of potential antifibrotic activity. The morphological examination of liver bioptate is a "gold standard" in assessment of liver fibrosis stage. However it is an invasive procedure and has several limitation such as "sampling error". Therefore several biochemical blood tests for liver fibrosis have been evaluated which are less invasive and give possibility of long-term monitoring of the course of disease and possible changes caused by treatment. The non-invasive markers of liver fibrosis include extracellular matrix components (ECM) as well as non-ECM biochemical panels (FibroTest, Forns index, APRI). Significant progress in diagnostics and treatment confirmed the reversibility of liver fibrosis. However, reversibility of cirrhosis still becomes controversial. Further investigations of antifibrotic drugs and settlement of proper biochemical blood panel for better monitoring of possible disease regression are needed.

Antiviral Agents↗

[Genealogic study of hypertrophic cardiomyopathy in the Czech population].

In order to test the type of heredity and to assess further genealogical characteristics in our population the authors examined 105 families with hypertrophic cardiomyopathy. The families were subjected to clinical, electrocardiographic and echocardiographic examination of relatives (72% grade 1 relatives) as well as to a genealogical and psychological examination. For the proband's siblings the empirical risk of disease was 24%, in male probands it wts four times higher for brothers than sisters, in female probands it was three times higher in sisters. The sex ratio of six siblings in men was 20:4, in women 3:14. For children the risk was substantially higher in youner probands (under 30 years risk 40%, above 51 years 6.7%). The proband's parents were affected in 28%, fathers almost twice as frequently in male probands, and equally frequently in female probands. Fitness (reproduction fitness, f) was substantially reduced in the entire group, in isolated and familial cases and in different age groups, more in women than in men. The gene penetrance (assuming monofactorial heredity) was estimated by the method of definite carriers as 50%. Earlier manifestations (anticipation) and a more severe course of the disease was observed practically in all families with occurrence of the disease in more than 2 generations (influence of selection--sampling error). In our group the heredity in hypertrophic cardiomyopathies was not simple autosomal dominance, it was not possible to rule out heterogeny, phenocopy, sexual influence. On the other hand, the group was too small to make possible unequivocal conclusions and the data were not quite consistent with data in the literature. Genetic counselling, possibly DNA diagnosis, would be needed to elucidate heredity of this disease.

Adult↗

Viral hepatitis and cirrhosis.

Most of the knowledge of post-hepatitic cirrhosis comes from studies performed in the last five years on the hepatitis B antigen-related variety. The position of other types of hepatitis (particularly type A) as an aetiological factor in cirrhosis remains conjectural. In general, the post-hepatitic cirrhosis develops insidiously after a mild or unrecognised acute episode of hepatitis. General progress is slow. Early deaths are due to liver failure. Later, primary hepatocellular carcinoma assumes increasing importance. Needle biopsy of the liver is usually necessary to confirm the diagnosis of cirrhosis and to estimate the degree of activity. Sampling errors when such a small specimen of liver is obtained must be taken into account, when formulating a diagnosis and prognosis. Prednisolone therapy is usually given if the patient is symptomatic, biochemical tests are abnormal and the liver biopsy confirms active chronic hepatitis with or without cirrhosis. The evidence of benefit is not so strong as for other forms of active hepatitis and cirrhosis such as the lupoid type. The management of the cirrhosis is otherwise along orthodox lines.

Acute Disease↗

Importance of selected athletic trainer employment characteristics in collegiate, sports medicine clinic, and high school settings.

OBJECTIVE: We examined employer importance ratings of 35 employee characteristics in the collegiate, sports medicine clinic, and high school settings and made comparisons among these settings. DESIGN AND SETTING: All prospective employers were sent a survey. Of the 472 surveys mailed, 282 (60%) were returned, with a sample error rate of 1.9%. SUBJECTS: All prospective employers listed on the NATA position vacancy notices from January 1, 1994 to October 1, 1994. MEASUREMENTS: Employers were asked to rate 35 employee characteristics as "not important" " minimally important," " important." or "very important." Additionally, employers chose 1 of 15 job descriptors that best identified their position vacancy. These 15 descriptors were then categorized into collegiate, sports medicine clinic, and high school settings. Discriminant analysis and analysis of variance procedures were used to determine if the 35 employee characteristics differed across the 3 settings. RESULTS: The discriminant analysis produced 2 significant discriminant functions (P < .05) with 23 of the original 35 characteristics remaining in the analysis. The first function discriminated between the collegiate setting and the other settings, with the collegiate setting scoring the highest. The second function discriminated among all 3 groups, with the sports medicine clinic and high school settings scoring the highest and lowest, respectively. Additionally, the analyses of variance (ANOVAs) revealed that 21 of the characteristics remaining in the discriminant analysis differed across the 3 settings. CONCLUSIONS: Employers from all 3 settings rated educational program reputation, written recommendations, job interview performance, and NATA-BOC certification eligibility as important to very important. For the collegiate setting, 7 characteristics were rated above important and included such characteristics as possession of a master's degree and collegiate experience. For the sports medicine clinic, 8 characteristics were rated above important and included sports medicine clinic experience, high school experience, and sport-specific experience. Finally, for the high school setting, 5 characteristics were rated above important. These included NATA-BOC certification, a bachelor's degree, and high school experience.

Journal Article↗

Spontaneous arteritis and glomerulitis in mice. A comparison of light and electron microscopic renal changes in PN/n, NZB/BL, 101/MAC, and CBA/MAC mice.

Four PN/n mice between 12 and 17 months of age had fibrinoid necrosis of the renal arteries, but 32 mice up to the age of 17 months showed no consistent change in the media or intima of the renal arteries although perivascular cuffing with round cells was prominent from 9 months of age. Glomerulitis, indicated by increase in the mesangium on light microscopy, affected most mice over 7 months of age, and dense deposits on electron microscopy were present in most mice from 7 months of age. These changes occurred significantly more frequently than in CBA/MAC mice; the 101/MAC showed an intermediate frequency, and the pattern in a small sample of NZB/BL mice resembled that of the PN/n mice. Basement membrane thickening increased with age from 3 weeks in all of the strains but more often included dense deposits in PN/n mice. Splitting of the glomerular basement membrane in very young mice in all strains was not considered relevant and may have been developmental. Failure consistently to detect glomerulitis earlier by electron microscopy than by light microscopy was attributed to the greater sampling error of the former. Unidentified dense bodies in glomerular epithelial cells occurred at all ages in all strains, so the suggestion that they were virus particles relevant to the disease was not sustained. Intraobserver variation studies showed satisfactory repeatability for light microscopy and for dense deposits and basement membrane thickening, but the dense bodies were not detected with acceptable reproducibility, a difficulty partly due to technical variation.

Age Factors↗

Role of fine needle aspiration cytology in the diagnosis of goiter.

Enlargement of the thyroid gland is a common occurrence in most parts of the world especially in the iodine-deficient goiter belt areas. Vast majority of these lesions are benign but they invariably lead to a series of investigations among which FNAC plays a pivotal role. Although many studies have reported diagnostic accuracy of FNAC in detecting neoplasms, there have been few studies where the role of FNAC in the diagnosis of goiter along with their diagnostic pitfalls has been evaluated. The present study was undertaken to assess the accuracy of FNAC in diagnosis of goiter and to highlight its limitations and diagnostic pitfalls. 771 cases over a five-year period were retrieved from the files of Cytopathology Laboratory, Department of Pathology at the All India Institute of Medical Sciences, New Delhi. They included 733 cases where the cytological diagnosis was goiter or suggestive of goiter along with 38 cases in which the histological diagnosis was goiter while the cytological diagnosis was cystic change or neoplasm. FNAC with minimum of two passes were performed in each case and May Grünwald Giemsa and Papanicolaou stains were done. Histology was available in 192 cases. The cytological and histological concordance was determined and the FNAC smears and histological sections in cases showing discordance were reviewed. There was cytological and histological concordance 130/168 (77.38%) cases. In 34 cases (20.23%) no diagnosis could be offered because of cystic change. A false positive cytologic diagnosis of neoplasm was made in 4 cases. Presence of hurthle cell metaplasia, hyperplastic nodules and papillary hyperplasias were responsible for the false positive diagnoses. In 24 cases neoplasms were initially missed on FNAC of which 10 cases could be detected on review while 5 cases were considered unsatisfactory. Sampling errors were mainly responsible for these false negative diagnoses. FNAC is thus an accurate and reliable diagnostic tool for management of goiters provided strict adherence to adequacy criteria are maintained.

Adenoma↗

How accurate are lexile text measures?

The Lexile Framework for Reading models comprehension as the difference between a reader measure and a text measure. Uncertainty in comprehension rates results from unreliability in reader measures and inaccuracy in text readability measures. Whole-text processing eliminates sampling error in text measures. However, Lexile text measures are imperfect due to misspecification of the Lexile theory. The standard deviation component associated with theory misspecification is estimated at 64L for a standard-length passage (approximately 125 words). A consequence is that standard errors for longer texts (2,500 to 150,000 words) are measured on the Lexile scale with uncertainties in the single digits. Uncertainties in expected comprehension rates are largely due to imprecision in reader ability and not inaccuracies in text readabilities.

Adolescent↗

Surgery for colorectal cancer guided by radiodetecting probe. Clinical evaluation using monoclonal antibody B72.3.

Radioactive antibodies that react with tumour-associated antigens to "tag" antigen-positive tumour cell deposits were given to 20 patients with primary or recurrent colorectal cancer. The tumour associated antigen TAG 72-specific monoclonal antibody B72.3 labelled with 125-Iodine was used, and the radioactivity in the tumour was sought during operation with a hand-held gamma detecting probe. Tumour was detected by the probe in 7 of 15 patients with primary cancer, with a mean tumour: normal tissue ratio of 3.9, and in 4 of 5 patients with recurrent disease, with a mean tumour: normal tissue ratio of 2.0. Immunohistochemical analysis of surgical specimens confirmed the results of the intraoperative detection. The incidence of TAG 72-positive tumours (11/20, 55%), detected by immunohistochemistry, was lower than the 80% in the other series, possibly because of sampling errors or because the cases studied were uncomplicated with small primary tumours. Results obtained with the probe were instrumental in modifying the operation in two of the four "positive" patients with recurrences, allowing the removal of tumour masses that would otherwise have been overlooked.

Adenocarcinoma↗

The histopathology of pulmonary reactions to drugs.

Many pathologists and pulmonologists have trained and practiced in an era during which therapeutic options for patients have increased manyfold with regard to pharmacologic agents. Toxicity to the lung may be recognized as data accumulate in the form of case reports and clinical reviews to document the clinical and pathologic manifestations. For the histopathologist, paradoxically the more we learn the more difficult problems of interpretation become. Drug reactions previously described extensively at the autopsy now can be relatively easily interpreted in living patients with tissue obtained by open lung biopsy. This latter procedure is becoming less common with diffuse infiltrative lung disease in favor of the transbronchial biopsy in which sampling error abounds. There may be no disease or minimal change. The pathologic lesions may be duly noted and described, but then defy interpretation. An accurate differential diagnosis following biopsy may not solve the clinical problems for which a tissue diagnosis was sought. A specific diagnosis may be made that does not fit the clinical picture, or the real "answer" may be revealed distressingly later in the clinical-course or, more distressingly, at autopsy. The prudent histopathologist deals with such limitation by objectively stating the observable facets of tissue injury and synthesizing an interpretation. Notwithstanding the burgeoning literature on mechanisms of injury of toxic substances, the "state of the art" in 1990 for interpretation of pulmonary drug reactions still lies with the exacting judgment of experienced clinical physicians. Proper evaluation can result in exclusion of important mimickers of interstitial lung disease, usually infection and neoplasia; accurate categorization of tissue injury and comparison with known injurious responses to the drug in question may lead to a relatively specific diagnosis of drug-induced injury. Most drug reactions in the lung are classified as an interstitial pneumonia. This article illustrates and describes several interstitial reactions to injury that have few histologic features in common. However, because the lung can only react to injury in a limited number of ways, lesions that were thought at one time to be a specific clinicopathologic entity, for example, DIP, now evoke an ever-expanding differential diagnosis. In applying diagnostic criteria emphasis must be placed on the areas of overlap among tissue reactions as well. Specific agents may cause changes that are described as common for that agent, but a given patient may react with a variation or in a distinctly uncommon manner. There is enormous potential in this field for the laboratory investigation of drug injury.(ABSTRACT TRUNCATED AT 400 WORDS)

Amiodarone↗

Cytology of lumpectomy specimens.

Residual microscopic disease after lumpectomy may cause significant local recurrence. This study evaluated the use of touch preparation cytology to assess lumpectomy margins. For 90 specimens, the findings on Diff-Quik-stained touch preparations (rendered intraoperatively within 15 minutes after the lumpectomy) were correlated with the gross findings, frozen-section results and, later, the findings in the permanent histologic sections. Three specimens were cytologically unsatisfactory, 68 yielded benign findings, and 19 were suspicious or diagnostic for malignancy. The margins showed tumor involvement in 5 lumpectomy samples by gross examination, in 13 by frozen-section evaluation and in 17 by the study of permanent sections. Touch preparation cytology was putatively falsely positive in two cases while frozen-section evaluation was falsely negative in four cases. Cytology had a sensitivity of 100%, a specificity of 97.1% and a diagnostic accuracy of 97.7%. These results demonstrate that touch preparation cytology rapidly and reliably evaluates lumpectomy margins and can overcome some sampling errors and artifacts related to frozen-section analysis. Touch preparation cytology is now being used to complement frozen-section evaluation of lumpectomy margins as part of a protocol aimed at reducing the local recurrence rate.

Biopsy↗

Characterization of musculoskeletal masses using dynamic Gd-DTPA enhanced spin-echo MRI.

Early studies evaluating the utility of Gd-diethylenetriamine pentaacetic acid (DTPA) enhanced MR imaging for characterization of musculoskeletal masses have demonstrated inconsistent and often conflicting results. In this study a new method, dynamic Gd-DTPA enhanced rapid acquisition spin echo MR imaging, was implemented in the evaluation of 18 musculoskeletal lesions and the enhancement features of these lesions were analyzed. Lesions were evaluated before, during, and sequentially following bolus Gd-DTPA injection. Analysis of intensity, volume, timing of onset, progression, uniformity, and pattern of enhancement did not demonstrate significant differences between benign (n = 8) and malignant (n = 10) masses. Significant variations in enhancement were noted in different regions within these masses, which limits the utility of previous dynamic contrast enhanced methods that provide only a single imaging slice for analysis, and are therefore subject to sampling error. This pilot study indicates no advantage for using dynamic Gd-DTPA enhanced imaging for qualitative lesion characterization.

Adolescent↗

Antimyosin imaging in cardiac transplant rejection.

Fab fragments of antibodies specific for cardiac myosin have been labeled with indium-111 and injected intravenously into animals and into patients with heart transplants. The antibodies, developed by Khaw, Haber, and co-workers, localize in cardiac myocytes that have been damaged irreversibly by ischemia, myocarditis, or the rejection process. After clearance of the labeled antibody from the cardiac blood pool, planar imaging or single photon emission computed tomography is performed. Scintigrams reveal the uptake of the labeled antimyosin in areas of myocardium undergoing transplant rejection. In animal studies, the degree of antimyosin uptake appears to correlate significantly with the degree of rejection assessed at necropsy. In patients, the correlation between scans and pathologic findings from endomyocardial biopsy is not as good, possibly because of sampling error in the endomyocardial biopsy technique. The scan results at 1 year correlate with either late complications (positive) or benign course (negative). Current limitations of the method include slow blood clearance, long half-life of indium-111, and hepatic uptake. Overcoming these limitations represents a direction for current research. It is possible that from these efforts a noninvasive approach to the diagnosis and evaluation of cardiac transplantation may evolve that will decrease the number of endomyocardial biopsies required to evaluate rejection. This would be particularly useful in infants and children.

Animals↗

Plasmodium berghei ookinete densities in three anopheline species.

Plasmodium berghei ookinete kinetics and densities were examined in the blood meals of 3 species of Anopheles mosquitoes fed simultaneously from a gametocytemic mouse. Simple techniques were developed for estimating relative and absolute ookinete densities within individual mosquito blood meals. The kinetics of ookinete formation were similar in all 3 species, with peak ookinete densities occurring from 12 to 24 hr postingestion. Ookinete densities consistently were lower in Anopheles stephensi than in Anopheles albimanus or Anopheles freeborni and could not be accounted for by species differences in blood meal volumes or gametocyte densities. Likely explanations involve species differences in blood meal hemolysis or sampling error as the result of ookinete emigration from the blood meal.

Animals↗

[Colonic polyps: clinical and practical implications].

Among colorectal polyps, various forms of neoplastic or non-neoplastic lesions are distinguished by histology. Most accumulated knowledge suggests that the majority of cancer of the colon arise in pre-existing benign neoplastic polyps (adenoma-carcinoma sequence). Because of the risk of cancer being already present, all adenomatous polyps must be removed in toto. The carcinoma may occupy only a small area of the polyp, and therefore, forceps biopsies are inappropriate due to the sampling error. Since patients with polyps detected by rectosigmoidoscopy often have further polyps in the remaining part of the colon, complete examination of the whole colon is required. Follow-up examinations are indicated, because the risk of developing new polyps is high. Studies of the life history of the adenoma-carcinoma sequence suggest that interval of complete large-bowel follow-up may be about 5 years. The policy of polypectomy and follow-up examinations should be possible to prevent the development of colorectal cancer.

Cell Transformation, Neoplastic↗

Flow cytometric and histomorphometric analysis of limitations of clinical breast cytomorphometry.

The clinical value and limitations of a previously described cytomorphometric method, based on nuclear size and anisonucleosis, for evaluation of routine fine-needle aspiration of the breast were assessed in a series of 313 histologically investigated primary breast lesions. Limitations were analyzed by histomorphometry and DNA flow cytometry in 116 consecutive cases of histologically confirmed breast carcinoma. Eighty per cent of histologically proven malignant tumours were classified cytomorphometrically as malignant and no false-positive results were encountered. For benign lesions a benign cytomorphometric classification was reached in 66% of the cases. Histomorphometry showed that on the whole the assignment of histologically malignant tumours to a non-malignant cytomorphometric classification was determined by smaller nuclei and not by sampling error. Tumours assigned to a malignant cytomorphometric classification had on average significantly higher DNA indices than did tumours not assigned to a malignant cytomorphometric classification (P less than 0.001). The mean-nuclear areas in cytomorphometry and histomorphometry were strongly correlated with DNA indices indicated by DNA flow cytometry (P less than 0.001 for both). The present findings show that this cytomorphometric method is appropriate for routine quality control of a cytological diagnosis of malignancy in FNA of the breast. However, an inconclusive result in 15-25% of the tumours is inevitable.

Aneuploidy↗