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PubMed1995

The urea breath test: a non-invasive clinical tool for detecting Helicobacter pylori infection.

The urea breath test exploits the urease enzyme of Helicobacter pylori. The hydrolysis of labelled urea releases labelled carbon dioxide that is excreted in the breath. Distribution of urea throughout the stomach prevents sampling errors and allows for semiquantitative assessment of the extent of Helicobacter pylori infection. The urea breath test is very specific and sensitive and can be proposed as the method of choice for detecting Helicobacter pylori infection in ulcer patients before and after eradicating treatment as well as in epidemiological studies.

Breath Tests↗
PubMed1994

Evolution of a computer program for classifying protein segments as transmembrane domains using genetic programming.

The recently-developed genetic programming paradigm is used to evolve a computer program to classify a given protein segment as being a transmembrane domain or non-transmembrane area of the protein. Genetic programming starts with a primordial ooze of randomly generated computer programs composed of available programmatic ingredients and then genetically breeds the population of programs using the Darwinian principle of survival of the fittest and an analog of the naturally occurring genetic operation of crossover (sexual recombination). Automatic function definition enables genetic programming to dynamically create subroutines dynamically during the run. Genetic programming is given a training set of differently-sized protein segments and their correct classification (but no biochemical knowledge, such as hydrophobicity values). Correlation is used as the fitness measure to drive the evolutionary process. The best genetically-evolved program achieves an out-of-sample correlation of 0.968 and an out-of-sample error rate of 1.6%. This error rate is better than that reported for four other algorithms reported at the First International Conference on Intelligent Systems for Molecular Biology. Our genetically evolved program is an instance of an algorithm discovered by an automated learning paradigm that is superior to that written by human investigators.

Amino Acid Sequence↗
PubMed1995

Change in karyotype between diagnosis and first relapse in acute myelogenous leukemia.

We compared karyotype at first relapse with presenting karyotype in 212 patients with AML seen at MD Anderson Cancer Center (Houston, TX, USA) between 1975 and 1994. In 38% the karyotypes at diagnosis and relapse were identical. A stable karyotype was most frequent (70%) among patients who presented without cytogenetic abnormalities, suggesting that the finding of a normal karyotype is usually not due to sampling error. In contrast, a finding of insufficient metaphases at diagnosis was repeated at relapse in only 6% of cases. A change in karyotype occurred in 67% of 101 patients who presented with an abnormal karyotype and had sufficient metaphases for evaluation at relapse. The great majority of changes involved clonal evolution, clonal devolution (regression), or both; a purely normal karyotype and unrelated clones were seen in 11 and three of the 101, respectively. Change in karyotype between diagnosis and relapse and type of change were unrelated to remission duration. The only group in which karyotype at relapse vs that at diagnosis had a possible bearing on achievement of second CR were patients who presented with abnormalities other than inv(16), t(8;21) or t(15;17) and who at relapse had only normal metaphases; such patients had higher CR rates than comparable patients who retained their presenting abnormalities.

Chromosome Aberrations↗
PubMedDate not supplied

MR imaging of adult supratentorial astrocytomas: an attempt of semi-automatic grading.

Using multiple regression analysis, six MR parameters were correlated with three histological grades among 43 proven adult supratentorial astrocytic gliomas to ascertain important MR parameters and their optimal contributions. Analysis revealed that two parameters, border definition and tumor hemorrhage, were unreliable. Using the remaining four parameters an equation was derived: Tumor grade = 0.32 (ring enhancement) +0.29 (degree of contrast enhancement) +0.13 (heterogeneity) +0.12 (edema) +0.41. Ring enhancement was the most reliable predictor of tumor grade, followed by degree of contrast enhancement. The maximum accuracies of the "semi-automatic" approach using this equation for predicting low-grade astrocytomas, anaplastic astrocytomas, and glioblastoma multiforme were 91%, 83%, and 88%, respectively. Although "semi-automatic" grading provided relatively high accuracy, possible sampling errors and some atypical cases reduced such accuracy.

Adult↗
PubMedDate not supplied

Discordance between cytologic and histologic reports in cervical intraepithelial neoplasia. Results of a one-year audit.

In order to investigate the factors contributing to cases in which the cytology and histology reports of cervical intraepithelial neoplasia (CIN) differ, we assessed the impact of careful review of the biopsy and its corresponding cervical smear. In a one-year audit of all cervical biopsies we found that 18.8% of biopsy-smear pairs disagreed by at least two grades of CIN. Following review the mismatch rate fell by 47%, mainly due to a drop in the number of cases in which the smear showed less severe CIN than did the biopsy. The proportion of cases in which the cytologic impression of CIN was greater than the histologic was changed little. The fall in the mismatch rate was seen after review of the smears, while a similar review of the histology did not alter the rate of mismatch. Neither the presence of koilocytotic changes on either cytology, histology or both, nor the size of the biopsy (punch vs. cone/hysterectomy) influenced the occurrence of such discrepancies. A similar review of the smears and biopsies of matching cases of CIN revealed no significant changes. This suggests particular difficulties of interpretation in the mismatching cases. In those cases with persistent mismatch an additional element of sampling error must be assumed to be the main cause even though all smears were considered of adequate quality.

Biopsy↗
PubMed1993

Microsporidia in the small intestine of HIV-infected patients. A new diagnostic technique and a new species.

OBJECTIVES: To determine whether microsporidian infections occur in Australian patients infected with human immunodeficiency virus (HIV), to assess the incidence, and to discuss microscopic detection methods. DESIGN AND PATIENTS: 180 consecutive HIV-infected patients (109 with chronic diarrhoea and 71 with other indications) underwent upper gastrointestinal tract endoscopy and pinch biopsies of the second part of the duodenum. The biopsies were handled by a protocol: four levels, with haematoxylin and eosin stain (H&E) at each level, periodic acid Schiff reagent after diastase (DiPAS) and auramine stain at the second level, and Warthin-Starry (WS) stain and cytomegalovirus early antigen immunoperoxidase study at the third level. Electron microscopy was carried out on samples from the first 95 patients, and thereafter from selected patients. SETTING: The patients came from the HIV Medicine Unit of a teaching hospital and from the practice of a gastroenterologist. MAIN OUTCOME MEASURES: Diagnosis of microsporidia was to based on the H&E stain, with electron microscopy as the definitive test because the microsporidia are often difficult to see with H&E. Empirically, the WS stain was found to stain the microorganisms and it replaced electron microscopy during the study as the screening diagnostic test. RESULTS: Microsporidia were present in 36 of the 109 patients with diarrhoea (33%) and one of 71 patients without diarrhoea. The WS stain in all cases showed developing spores in the enterocytes and in four cases in macrophages as well. The H&E stain showed non-specific duodenitis and was not diagnostic in some cases. Electron microscopy on samples from the first 95 consecutive patients showed 100% concordance with the WS stain. In 33 cases, electron microscopy showed the multinucleated plasmodia and the spores of Enterocytozoon bieneusi and in the four cases confirmed the spores in macrophages and showed a new Encephalitozoon-like species with a septate parasitophorous vacuole. Other causes of duodenal infection were cytomegalovirus (11 cases), mycobacteria (8), cryptosporidia (8) and Giardia lamblia (5). CONCLUSION: E. bieneusi was the commonest microorganism found in our series of 180 consecutive patients. The actual prevalence of the two microsporidia species within the HIV-positive population and general community awaits further study. The WS stain provides a sensitive diagnostic test for the presence of E. bieneusi and the new Encephalitozoon-like species, avoiding the cost and potential sampling error of electron microscopy. The detailed ultrastructure and taxonomy of the new species requires further study.

AIDS-Related Opportunistic Infections↗
PubMed1995

Somatic mutations detected by mini- and microsatellite DNA markers reveal clonal intratumor heterogeneity in gastrointestinal cancers.

We investigated clonal intratumor heterogeneity by comparing different areas of each tumor in 20 gastrointestinal cancers from female patients (1 esophageal cancer, 5 stomach cancers, and 14 colorectal cancers). In all 19 cases informative for X-inactivation analysis with the M27 beta and/or the phosphoglycerate kinase probes, the tumors were clonal. Separate areas from a given tumor showed identical X-inactivation patterns, providing evidence for its single-cell origin. Of 20 cancers, 11 showed p53 gene mutations (base pair insertions, point mutations, and one case of a base pair deletion) in exons 5-8. A particular p53 gene mutation was identical in all tumor areas investigated per case. The minisatellite probes detected loss of heterozygosity or new mutant alleles at 1p33, 1q21, 5q35, 17p13, or 18q21. In seven cases mutations at particular loci were restricted to one or two areas per tumor, while in another seven cases they were common to all tumor areas. Loss of heterozygosity or new alleles detected at the microsatellite loci D2S123, D3S1611, D5S107, D17S261, or D18S34 [(CA)n repeats] were common to all tumor areas in 7 of 19 cases. In another seven cases, however, microsatellite mutations at these loci were restricted to one to three areas per tumor. Tracing clonal intratumor heterogeneity would permit one to study the hierarchy of mutational events in cancers where no premalignant lesions can be harvested. Most important, our study indicates that clonal intratumor heterogeneity might lead to sampling errors in the molecular diagnosis of cancer biopsy specimens when using mini- or microsatellite markers.

Alleles↗
PubMed1994

Renal disease in POEMS syndrome: report on a case and review of the literature.

POEMS syndrome is a multisystem disorder associated with plasma cell dyscrasias. This report describes a patient with POEMS-associated renal disease and reviews the literature on biopsy-proven renal involvement in POEMS syndrome. Our patient had glomerulonephritis with membranoproliferative features on light-microscopy without characteristic findings on immunofluorescence, and with ultrastructural evidence of glomerular microangiopathy. Ultrastructural evidence of microangiopathy was also found in vasa nervorum. In 20 other cases of POEMS-associated renal disease, 16 had glomerular disease. Light-microscopy showed membranoproliferative-like glomerulopathy in 14 patients and glomerular microangiopathy in two. Ultrastructural evidence of microangiopathy was present in all 15 patients in whom electron-microscopy was done. Thus, in most patients with POEMS-associated glomerular disease a characteristic lesion is present with evidence of endothelial injury. As endothelial damage is also found in endoneural vessels, generalized endothelial injury may play a role in non-renal manifestations of POEMS syndrome. In previous reviews manifestations of the POEMS syndrome were similar for patients with or without myeloma. Among patients with biopsy-proven glomerular disease, however, myeloma patients are underrepresented. Whether this represents a sampling error or has true pathophysiological significance remains to be established.

Adult↗
PubMed1994

Telepathology is available for transplantation-pathology: experience in Japan using an integrated, low-cost, and high-quality system.

We examined the validity and accuracy of telepathology service in the histological diagnosis of biopsy specimens from human transplanted kidney and liver. The still video images of paraffin sections were transmitted via a two-way telephone by use of a digitized telephone network (Integrated Service Digital Networks, 64 kbits/sec). The images were displayed on monitors and diagnosed by an expert pathologist at Tottori University. The quality of transmitted still images was sufficient for the diagnosis, especially at higher magnifications. The average number of transmitted images was 6.2 in the kidney cases and 7.4 in the liver cases. The average time taken for examination of a case was 13 min (range 10 to 16 min). Of 12 biopsy specimens from transplanted kidneys, 10 were adequately diagnosed with the system. Sampling errors caused inadequate diagnosis in a case of cyclosporin tubulopathy, the still images of which were not transmitted. An expert pathologist rendered the diagnosis in a case showing mesangial sclerosis, which was later diagnosed as possible recurrent glomerulonephritis through direct microscopy. Biopsy specimens from 10 liver transplants were also tested using archival materials. Although the etiology of hepatitis could not be determined in one case, diagnoses by telepathology well agreed with the reported diagnoses made through direct microscopy. Telepathology may be an effective way to provide on-line consultations in transplantation pathology, especially for transplant teams lacking expert pathologists.

Adolescent↗
PubMedDate not supplied

Fine needle aspiration biopsy in the diagnosis of lymphadenopathy in 1,103 patients. Role, limitations and analysis of diagnostic pitfalls.

Fine needle aspiration biopsy (FNAB) is widely used for the assessment of various lesions. The results of FNABs of lymph nodes on 1,103 patients, performed over a 14-year period, from 1978 to 1992, are presented. The patients ranged in age from 1 to 90 years. Cervical nodes were the site sampled most frequently (47%). Of all the aspirates, 593 were diagnosed cytologically as malignant, 61 as suspicious for malignancy and 329 as benign. The material was classified as unsatisfactory in 120 cases. Aspirates from supraclavicular nodes were most likely to be malignant (85%), followed by those from deep nodes (67%). The most challenging lesions to assess using FNAB were lymphomas, accounting for 15 of the 23 false negatives. Most of these were related to difficulty in the interpretation of well-differentiated neoplasms in the early years of this study, prior to the use of immunocytochemistry. Sampling errors accounted for eight false-negative diagnoses; they included all the cases of metastatic carcinomas that had been missed. There were only three false-positive diagnoses; two of these involved the misinterpretation of lipid-rich lesions as metastatic clear cell carcinomas. The results of this study support the accuracy of FNAB and its value in investigating lymphadenopathies. FNAB of nodes provides a high level of diagnostic accuracy, as shown by the 3.4% false-negative and 0.9% false-positive rates. Lymphoid marker studies of cytologic material greatly enhance our ability to diagnose and properly classify lymphomas and reduce the false-negative rate.

Adolescent↗
PubMed1995

Flow cytometry provides rapid and highly accurate detection of antisperm antibodies.

OBJECTIVE: Immunobead testing (IBT), the current standard for antisperm antibody detection, is time consuming and somewhat subjective. To overcome these limitations and maintain accuracy, we studied an immunofluorescent assay using flow cytometry. DESIGN: A validation study comparing flow cytometry to IBT in the detection of serum antisperm antibodies. SETTING: Flow cytometry laboratory. PATIENTS: Sera from 37 men after vasectomy (test) and sera from 35 fertile men (control). MAIN OUTCOME MEASURE: Test serum with and without immunoglobulin (Ig)G, IgA, and IgM antisperm antibodies as defined by IBT were analyzed by flow cytometry. Sensitivity and specificity of flow cytometry was calculated by defining the IBT as the true result. RESULTS: Flow cytometry identified 22 of 22 sera that were IgG positive (100% sensitivity), 12 of 14 sera that were IgA positive (86% sensitivity), and 4 of 4 sera that were IgM positive (100% sensitivity). Overall, 22 of 37 men were positive for antisperm antibodies. The flow cytometry correctly identified 71 of 71 negative sera (100% specificity). Fluorescence intensity values from the 37 study patients significantly correlated with immunobead binding to the head region and to the entire (more than one) region. CONCLUSIONS: Detection of IgG, IgA, and IgM antisperm antibodies by flow cytometry is highly sensitive and specific. In addition, flow cytometry is able to assess thousands of sperm rapidly and accurately, reducing sampling error and technical time.

Antibodies↗
PubMedDate not supplied

Loss of variability in Graves' disease: stimulatory TSH-receptor antibodies bind to the TSH-receptor in a continued, non-pulsatile and non-chaotic fashion.

Thyroid-stimulating hormone (TSH) regulates thyroid growth and differentiated function by binding to the TSH-receptor (TSH-R). In Graves' disease, hyperthyroidism and goiter growth are thought to be mediated by prolonged, continued activation of the TSH-R by TSH receptor-stimulating antibodies (TSAb). However, continuous experimental stimulation of the TSH-R with TSH or TSAb leads to a desensitization of the thyrocyte with a decrease of thyroid function in vitro and in vivo. In order to clarify this discrepancy we determined serum levels of TSH-binding-inhibiting immunoglobulins (TBII) in 10 patients with GD every 10 minutes over 6h (patients 1 to 5, group A) and over 24h (patients 6 to 10, group B) using a commercially available radio ligand receptor assay (TRAK, Henning Berlin, FRG). Visual and computer analysis revealed some variation of TBII serum levels but no obvious pattern indicative of circadian variation nor major secretory peaks could be distinguished. Variation of TBII serum levels were within or only slightly above intraassay CV. Data were tested in order to decide whether the observed fluctuations are of chaotic (deterministic) or of stochastic (random) origin. In none of these tests did we find evidence for chaos in the data suggesting that the observed fluctuations reflect other sources of noise such as sampling errors or intraassay variation. We conclude that in Graves' disease, patients are rendered hyperthyroid by continued, non-pulsatile and non-chaotic binding of stimulatory antibodies to the TSH binding site of the TSH-R.

Adult↗
PubMed1994

Fine-needle aspiration of normal thyroid tissue may result in the misdiagnosis of microfollicular lesions.

BACKGROUND: Inadvertent sampling of normal thyroid tissue surrounding a nodule may occur when clinically inexperienced personnel perform fine-needle aspiration (FNA) or when a nodule is small. Because the cytologic characteristics of normal thyroid tissue are not well known, we prospectively studied 42 patients undergoing thyroidectomy. METHODS: FNA was performed from the grossly normal contralateral lobe during thyroidectomy. Cytopathologists examined the slides without knowing the source of the tissue. RESULTS: FNA of grossly normal thyroid tissue was adequate for interpretation in 32 of 42 patients, and in nine of 42 cases it was interpreted as unremarkable. However, the remaining specimens were classified as microfollicular lesions (18), mixed macromicrofollicular lesions (three), Hürthle cell lesion (one), and papillary thyroid carcinoma (one). CONCLUSIONS: FNA of grossly normal thyroid tissue suggested a microfollicular lesion in 18 (56%) patients, a result that would raise the possibility of a follicular carcinoma and often lead to the recommendation for operation. When FNA is performed, normal thyroid tissue surrounding a nodule should be avoided, and the possibility of a sampling error should be considered when a microfollicular pattern is obtained in a patient with a small nodule.

Biopsy, Needle↗
PubMed1993

The A1 allele at the D2 dopamine receptor gene and alcoholism. A reappraisal.

OBJECTIVE: An allelic association between the TaqI "A" system A1 allele at the D2 dopamine receptor locus (DRD2) and either alcoholism or severe alcoholism has been proposed. Our purpose was to evaluate whether, based on all of the accumulated evidence, this association could be considered to be proven. DATA SOURCES: We considered data from all published reports of DRD2 allele frequency in alcoholics, controls, or both. STUDY SELECTION: We concentrated on the issue of replication. We therefore considered all data reported (on white samples, because DRD2 allele frequency varies by race and ethnicity) since the first report by Blum et al in 1990. DATA SYNTHESIS: We analyzed the set of data for differences in allele frequencies between alcoholics and controls, and for heterogeneity among samples. We also investigated the influence of the data from the first group to report an association (including a subsequent report from that group) on the findings. Our analysis shows that, when all studies subsequent to the original study are considered, there is no significant difference in DRD2 A1 allele frequency between alcoholics and controls, there is significant heterogeneity among reported alcoholics and reported controls, and there is no significant difference in DRD2 A1 allele frequency between severe and not severe alcoholics. Also, the two reports of Blum et al account for all of the (nonsignificant) differences seen between controls, alcoholics, and severe alcoholics. CONCLUSIONS: In general, heterogeneity among studies (for alcoholics or controls) is considerably greater than differences between alcoholics and controls overall. The findings to date can best be explained by more conservative interpretations than a confirmed physiologically important allelic association between DRD2 alleles and alcoholism. These other possibilities include sampling error and ethnic variation in those studies that individually showed a large effect.

Alcoholism↗
PubMed1993

[Accuracy of frozen section in diagnosis of ovarian tumors].

One hundred and thirty-six frozen section of ovarian tumors were compared with the paraffin sections during 1986-1992. The final histological diagnosis were: benign 52 cases, borderline malignant 22 cases, and malignant 62 cases. The accurate rate of the frozen section method for malignant was 93.5%, benign was 100.0% and borderline malignant was 77.2%. Predictive values were computed: 100.0% for malignant, 85.0% for borderline malignant and 89.6% for benign disease. Analysis of the 9 false negative revealed that 8 cases were sampling error and most occurred in mucinous borderline tumors. Our data showed that the frozen section was a relative accurate and reliable method for diagnosis of ovarian tumor during operation.

Adolescent↗
PubMed1993

Intraoperative frozen section consultation: an analysis of accuracy in a teaching hospital.

This is a retrospective quality assurance study of all frozen sections done at The Aga Khan University Hospital during a six year period (1986 to 1991). There were 1,031 frozen sections out of a cumulative total of 42,985 surgical specimens (2.39%). Nine hundred and severity-six (94.66%) were concordant. In 92 (8.9%) fresh specimens were brought from other hospitals of Karachi, in 37 cases (3.58%) the diagnosis was deferred till the evaluation of permanent paraffin sections and 18 (1.74%) were discordant with 7 (0.67%) false positive and 11 (1.06%) false negative. Among the discordant cases, 9 were attributed to misinterpretation, 7 due to sampling errors and 2 due to technical reasons. Some of these errors might have been avoided, but appear to be an irreducible minimum.

Frozen Sections↗
PubMed1994

Intraoperative consultation of ovarian neoplasms.

A review of 313 intraoperative consultations and/or frozen section evaluations of neoplasms of the ovary was conducted. The intraoperative diagnosis of benign or malignant was compared with the diagnosis found at permanent section. Only six cases were deferred to permanent section. The overall accuracy was 93.9%. The sensitivity was 72.7%, and this was explained by the high proportion of borderline or low malignant cell tumors in this series. The specificity and predictive values were in excess of 95%. Thirteen cases were diagnosed incorrectly at intraoperative consultation. Eight of these were judged to be sampling errors, one was due to poor technical quality, and four were attributed to interpretation errors. Intraoperative consultation is, and should continue to be, a valuable tool in the evaluation of ovarian neoplasms.

Diagnostic Errors↗
PubMed1994

Renal effects of nonionic contrast media after cardioangiography.

A prospective double-blind randomized cardioangiographic study with iopentol and iohexol was performed in 60 patients. Glomerular filtration rate (GFR) was assessed by serum values of creatinine and beta 2-microglobulin (beta 2-MG), estimated creatinine clearance (CCr) according to Cockroft & Gault's formula, and 24 hour CCr. The urinary excretion of albumin, beta 2-MG, and of the renal tubular enzymes alkaline phosphatase (ALP) and N-acetyl-beta-glucosaminidase (NAG) was also measured. Contrary to what has been found after i.v. injections, GFR was reduced by both nonionic contrast media. Serum creatinine (S-Cr) was increased by more than 25% in 6 patients, 3 in each group. CCr was more sensitive than S-Cr and S-beta 2-MG, but this method is less precise because of risk of urine sampling errors. Estimated CCr gave no additional information to S-Cr. The urinary excretion of NAG and ALP was increased. No clinically significant differences between iopentol and iohexol were detected. No correlation was found between the changes in tubular function parameters and changes in GFR. Twenty patients were on calcium channel blockers before the investigation, but this had no protective effect on the renal function parameters.

Adult↗