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Immunogenic effects of culture-derived exoantigens of Cooperia punctata on calves before and after challenge exposure with infective larvae.

The parasitic stages of Cooperia punctata were cultivated in vitro, and the incubation fluid from these stages containing exoantigen (ExoAg; metabolites, secretions, excretions) was diafiltered (retaining material of approximate molecular weight greater than 10,000), concentrated, and lyophilized. Using serum of calves immune to C punctata, ExoAg activity was verified by agar gel immunodiffusion. The ExoAg was combined with adjuvants and was inoculated into calves. Results of preliminary experiments indicated that the ExoAg had potent biological activity capable of inducing severe respiratory distress and death. Subsequently, however, improved inoculation procedures and combination of ExoAg with aluminum hydroxide gel or Freund complete adjuvant consistently prevented this reaction in 25 calves. In helminth-free calves, the ExoAg induced marked eosinophilia, which generally was greater during the ExoAg-exposure period than after challenge exposure with infective larvae. Of 27 calves exposed to the various ExoAg inoculation schedules, 12 had nematode reductions greater than 80%, 10 had less than 16% reduction, and 5 had reductions between 39 and 72%. This polarization of the nematode recovery data generally thwarted statistical difference in overall consideration of all ExoAg inoculation schedules. Additional manifestations of resistance, ie, prolonged prepatent period, reduced patent period, reduced number or lack of nematode eggs passed in feces, and reduced nematode length, were observed in calves of certain ExoAg inoculation schedules. In vitro blastogenic responses of blood lymphocytes was observed in calves exposed to ExoAg. Quantitatively, this cell-mediated immune response to ExoAg was as great as or greater than that after subsequent challenge exposure with infective larvae. Intradermal inoculation of ExoAg into a calf resistant to C punctata induced delayed-type hypersensitivity. However, this reaction to ExoAg was not observed in nonimmunized, helminth-free calves used as controls. Humoral antibodies against ExoAg were detected by an agar gel immunodiffusion test. Calves exposed to ExoAg always seroconverted and usually remained seropositive until necropsy. There were no false-positive results; however, ExoAg did not consistently coprecipitate (by agar gel immunodiffusion) with serum from infected calves that were not exposed to ExoAg.

Animals↗

Role of 67gallium citrate scanning in the management of non-Hodgkin's lymphoma.

67Gallium scans were performed as part of the initial evaluation in 45 patients with non-Hodgkin's lymphoma. Eighteen of these patients underwent staging laparotomy and splenectomy. In addition, scans were performed either shortly after therapy was completed or during subsequent followup in 10 patients. The initial scans were found most useful for patients with histiocytic lymphoma: in detecting sites of involvement above the diaphragm and the high para-aortic/mesenteric region, and when tumors were greater than 2 cm in diameter. The addition of 67Ga scanning to the pre-operative clinical evaluation reduced the number of incorrectly staged patients from 8 to 4. Reversion of previously positive 67Ga scans to negative in 3 patients with suspected persistent or recurrent disease was associated with fibrosis and no lymphoma when biopsied. Five other patients had histologically documented positive 67Ga scans post-therapy; in 1 the 67Ga scan was only definitive noninvasive procedure. Despite the occurrence of both false-positive and false-negative 67Ga scans, this procedure appears to be a useful supplement to the pretreatment evaluation of patients with non-Hodgkin's lymphoma, especially the histiocytic form. Confirmation of its ability to detect high para-aortic/mesentric involvement may subsequently result in a reduction of the number of staging laparotomies necessary. For the post-treatment followup of these patients 67Ga scans may prove to be valuable noninvasive investigation.

Abdominal Neoplasms↗

Detecting and excluding significant left main coronary artery narrowing by echocardiography.

Two-dimensional echocardiography (2-D echo) of the left main coronary artery (LMCA) was attempted in 50 patients undergoing arteriography to evaluate 2-D echo for recognition of significant stenosis of the LMCA. Although the echocardiographer was experienced and used rigorous technique, visualization of the LMCA adequate for making a judgment regarding lumen reduction was possible in only 37 patients (74%). Of the 10 studies with suspected positive findings for LMCA stenosis by 2-D echo, 4 yielded true-positive and 6 false-positive results. A study from 1 other patient with LMCA stenosis by angiography was erroneously interpreted as negative by 2-D echo. Analysis of arteriograms in the 6 patients with false positive 2-D echo readings failed to implicate significant proximal left anterior descending artery narrowing as the cause of the errors. Although 2-D echo was correct in indicating the presence or absence of LMCA stenosis in 30 of 37 patients, and the predictive value of a negative 2-D echo response was 96%, the noninvasive method appears to be inadequate as a screening test. Widespread use of the procedure is limited by the 26% failure rate for adequate studies in experienced hands, and the implications of the occasional false-negative finding. If LMCA stenosis is suspected by 2-D echo in a patient who needs arteriography, the special care given to this possibility by the arteriographer should not harm the patient.

Adult↗

The redox-cycling assay is not suited for the detection of pyrroloquinoline quinone in biological samples.

Based on the results of the so-called redox-cycling assay it has been claimed that various common foods and beverages as well as mammalian body fluids and tissues contain substantial quantities (microM) of free PQQ [M. Paz et al. (1989) in: PQQ and Quinoproteins (J.A. Jongejan and J.A. Duine, eds.) Kluwer Academic Publishers, Dordrecht, pp. 131-143 and J. Killgore et al. (1989) Science 245, 850-852]. However, by investigating samples from such sources with a biological assay of nM sensitivity, we could not confirm these claims. Analysis of the samples with procedures that proved adequate for the detection of PQQ adducts and conjugates gave equally negative results. To account for the positive response in the redox-cycling assay, as opposed to the negative results obtained by other methods, a search was made for those substances in these samples that caused the false-positive reactions. It was found that a number of commonly occurring biochemicals like ascorbic and dehydroascorbic acid, riboflavin and to a lesser extent pyridoxal phosphate, gave a positive response in the redox-cycling assay. The amounts of these interfering substances that were determined in the samples by independent methods could well explain the response. In separate experiments it was found that the effect of PQQ added to biological samples was obscured over an appreciable range of concentrations. For these reasons it must be concluded that the redox-cycling assay is not suited for the detection of PQQ in these samples. Any claims that are based on the results of this method should be disregarded.

Animals↗

Effects of pulmonary emphysema on QRS infarct size score.

Pulmonary emphysema can produce false-positive electrocardiographic (ECG) changes of anterior myocardial infarction (MI). This problem was not addressed in earlier studies of the Selvester 54 Criteria/32 Point QRS score for MI size. The purpose of this study was to examine an automated Hewlett Packard ECG Computer Language (HP-ECL) implementation of the QRS score in the following groups of subjects. Patients who had been studied for possible lung disease with pulmonary tests, including lung volumes, were divided into two groups: group 1 (n = 133), with abnormal tests (emphysema); and group 2 (n = 102), with normal tests (no emphysema). Two other groups were studied: group 3 (positive controls, n = 44), with greater than 3 QRS points for MI on ECG and documented coronary disease with wall motion abnormalities on angiography; and group 4 (negative controls, n = 146), 49 house staff and 97 clinically normal men. A frontal plane P axis greater than 65 separated 90% of patients with emphysema from those without. Of 133 patients with emphysema, 60 (45%) had greater than 3 QRS points for MI on ECG, mainly from Q criteria in aVL and V1-V3; decreased R criteria 1 in V2, V3, and V6; and abnormal R/S criteria in V4-V6. Using HP-ECL, the QRS score was readily modified so that when P axis was greater than 65 these MI size criteria were suppressed. This resulted in a more appropriate incidence of MI diagnoses: 2% (down from 45%) in emphysema patients, no change in specificity, and minor reduction in sensitivity to MI in infarct controls from 100% to 96%.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrocardiography↗

Usefulness of Q-wave response to exercise as a predictor of coronary artery disease.

In lead CM5, the Q-wave response to exercise has been reported as an effective index in predicting coronary artery disease (CAD) and CAD with left anterior descending (LAD) disease. The purpose of this study was to verify these findings when the Q wave was analyzed in lead CC5 in 135 patients. The sensitivity for abnormal ST depression was 77%, specificity 83% and predictive value 78%. The corresponding values for the abnormal Q-wave response (reduction or no change in Q-wave amplitude) were 70%, 61% and 59%. These differences (except sensitivity) were significant. When either a positive ST or Q-wave response was used, sensitivity, specificity and predictive value did not significantly increase compared with the ST segment alone. In addition, only 45% of normal subjects with false-positive ST depression had a normal Q-wave response (increase) and 57% of patients with false-negative ST responses had an abnormal Q-wave response. When a positive response for CAD with an LAD lesion and for multivessel CAD with LAD narrowing was defined as having a Q-wave reduction, the sensitivities were extremely low (15% and 17%), but both the specificities and the predictive values were 100%. Therefore, the Q-wave analysis in lead CC5 is no more sensitive for detecting CAD than the ST-segment response. However, when a decreased Q-wave amplitude is observed, multivessel CAD and LAD narrowing can be predicted.

Coronary Disease↗

Successful use of pooled sera to determine HIV-1 seroprevalence in Zaire with development of cost-efficiency models.

To determine the accuracy and cost efficiency of pooling sera prior to HIV-1 testing, sera from 8,000 Kinshasa factory workers and their spouses were screened individually (2.44% seropositive) and in 800 pools of 10 sera each. There were no false-negative or false-positive pools, resulting in a calculated seroprevalence estimate of 2.42%. Further testing of all sera in positive pools can identify HIV-positive individuals. These applications were modeled to compare the cost-efficiency of pooling with individual testing under different conditions. The results suggest that pooling provides an alternative test format for use in both developing and industrialized countries when the seroprevalence and/or the marginal cost of obtaining a sample are sufficiently low. For our cohort, testing only the pools for seroprevalence estimation resulted in a 78% cost saving compared with individual testing; pooling with subsequent identification of individual seropositives represented a 56% cost reduction.

Acquired Immunodeficiency Syndrome↗

A clinic-based system for monitoring the quality of techniques for the diagnosis of gonorrhea.

The author describes a clinic-based system that monitors the quality of techniques for diagnosis of gonorrhea by continuous comparison of the results of gram-strained smears of urethral and cervical specimens with the corresponding cultures. Discrepant results are immediately reviewed. During a two-year period, the system detected two defects in culture incubation, visual defects in a laboratory technician, and three unexplained reductions in cultural sensitivity. The system motivates clinicians and laboratory technicians to maintain a high level of quality control. In 11,474 comparisons of urethral smear and culture results, there was agreement in 96.9% while the smear alone was positive in 1.6% and the culture alone in 1.5%. Review of positive-smear-negative-culture discrepancies indicated that most smears judged "false-positive" were so classified on the basis of false-negative cultures. In study of 1,331 women, the endocervical smeras identified 60% (273/455) of those with positive culture discrepancies. Many of these may have represented false-negative cultures.

Clinical Laboratory Techniques↗

False-positive, follicular and irritant patch test reactions to metal salts.

853 hard metal workers were patch tested with nickel sulphate 5%, potassium dichromate 0.5% and cobalt chloride 1%, each in petrolatum. Non-allergic reactions appeared in 6.5% of the nickel tests, 13% of the chromium tests and 18.3% of the cobalt tests. Most of the individuals with positive, poral or pustular reactions were retested with serial dilutions of metal salts in pet. and in water. The accuracy of a positive initial nickel reaction was 83%, a chromium reaction 40% and a cobalt reaction 62%. The nonallergic reactions were partly reproducible and correlated with both the type of patch test material and with individual factors. Weak and moderately strong positive patch test reactions to metal salts may be irritant and should be checked with serial dilution tests or at least be retested. A reduction of the cobalt chloride concentration from 1% to 0.5% in the standard test material is discussed.

Chromates↗

Selective detection and enumeration of fecal coliforms in water by potentiometric measurement of lipoic acid reduction.

Water samples of various origins were inoculated into a specific coliform-selective lactose broth provided with lipoic (thioctic) acid, and the time evolution of the redox potential of the cultures was monitored during incubation at 41 degrees C by use of gold versus reference electrodes. Positive potential-time responses, i.e., 100-mV potential shifts recorded within 20 h of inoculation, were related to the initial number of fecal coliforms in the broth determined by control enumeration techniques, and the organisms responsible were isolated and identified by conventional procedures. A total of 30 samples of wastewater, 38 of surface water, 553 of groundwater, and 110 of drinking water were tested successively. A total of 240 natural water samples, including 172 groundwater samples, and 1 drinking water sample were found to be positive in the potentiometric test. The majority (i.e., 92.5%) of the relevant potentiometric detection times were shorter than 15 h, and 96% of these could be attributed to Escherichia coli. Fifteen hours corresponded to the limit for detecting 1 E. coli cell per 100 ml of water. About 78% of the potentiometric responses occurring after 15 h were induced by fecal coliforms other than E. coli (Enterobacter cloacae, Klebsiella pneumoniae, and Citrobacter freundii). Calibration curves relating detection times shorter than 15 h to fecal coliform (i.e., E. coli) concentrations were constructed for the natural water samples tested. There were minor variations in the average growth rate of the organisms in the relation to the contamination level of the water tested. The number of false-positive samples in the potentiometric test was equivalent to that of false-negative samples (groundwater or drinking water).

Drinking↗

Trypsinised human O erythrocytes in the detection of rubella-specific IgM by sera fractionation on sucrose density gradient and absorption with staphylococcal protein A.

Detection of rubella virus-specific IgM employing trypsin-treated human group O erythrocytes was evaluated using the method of sera fractionation on sucrose density gradients (SDG) and that of sera absorption with staphylococcal protein A. The former method proved to be highly specific and sensitive in confirming or excluding rubella by demonstration of specific IgM. In contrast, the latter method provided comparable results in only 71.43% of specimens tested by both methods while false-positive or -negative IgM results were obtained in the remaining 28.57% of specimens. In view of these results, therefore, it is recommended that all those specimens found positive for specific IgM by the protein A method must be confirmed by another procedure, possibly that of specific IgM reduction with 2-mercaptoethanol.

ABO Blood-Group System↗

Results of ophthalmosonometry and supraorbital photoplethysmography in evaluating carotid arterial stenoses.

A total of 263 patients underwent either periorbital ophthalmosonometry (Doppler ultrasound) or a combination of ophthalmosonometry and supraorbital photoplethysmography (SOPPG) to determine the presence or absence of a hemodynamically significant lesion (occlusion or greater than 50% reduction in lumen diameter). There were 522 vessels studied with Doppler ultrasound and 272 vessels with a combination of the two modalities. The tests were correlated with carotid arteriography to determine their accuracy. Overall accuracy of the Doppler ultrasound examination was 95%. A normal Doppler ultrasound examination was obtained in 367 vessels and arteriography confirmed the absence of a hemodynamically significant lesion in 93%. Of 155 vessels with an abnormal Doppler examination, 149 (96%) were proven on arteriography to have hemodynamically significant lesions. The Doppler ultrasound examination had a high incidence of false-negative examinations (26%) in those vessels that were between 50% and 99% stenotic, however. The SOPPG alone had a high incidence of false-positive examinations (19%); however, in 155 vessels with a normal SOPPG, 98% were proved to have no hemodynamically significant lesion. The combination of Doppler ultrasound and SOPPG was highly accurate in identifying patients with hemodynamically significant lesions. Of 97 vessels with such lesions, 96 (99%) had either an abnormal Doppler ultrasound examination or an abnormal SOPPG. In 240 vessels with concordant results of the Doppler ultrasound and SOPPG, the presence or absence of a hemodynamically significant lesion was accurately predicted in 235 (98%).

Arterial Occlusive Diseases↗

Evaluation of the usefulness of nitroblue tetrazolium reduction test (NBT test) for detection of bacterial infection in cancer patients.

False positivity of the NBT test in neoplastic diseases described by some authose may be a limitation in the use of the test for infection screening in cancer patients. For explaining this problem studies were performed in a group of 30 patients with various untreated malignancies without infection and in 20 of these with bacteriologically confirmed infections. The obtained results were compared with those in groups of normal persons without and with infection. Slightly modified Park method for spontaneous and stimulated NBT test was used. No significant differences between patients of both groups without infection were found. The increase in positivity of the test in presence of infection was lower in cancer patients than in normal subjects, however, it was non-significant. We did not observe any false-positive results in our patients, though one case of false negativity in myeloma is described separately. It is concluded that neoplastic disease does not cause, as such positivity of the NBT test. Because of similar response of NBT test to presence of infection, the NBT test is recognized as very useful for infection screening in cancer patients similarly as in normal persons.

Adult↗

[Echographic measuring of the length of the fetal femur in the screening for Down syndrome].

OBJECTIVE: Our purpose was to assess the value of sonographic measurement of fetal femur length in the second trimester, as a screening tool for Down's syndrome. STUDY DESIGN: We evaluated a consecutive series of fetuses scanned by a single sonologist at the time of amniocentesis between 15 and 19 weeks. The study group consisted of fetuses with Down's syndrome (N = 16); the control group comprised normal fetuses (N = 1163). A linear regression model of the normal femur length based on biparietal diameter (BPD), was established for our population; the ratios of measured to expected femur length for a viven BPD (FL M/E) were calculated in the two groups. To test statistical significance of observed differences between case and control population, unpaired t test was used. The ability of specific FL M/E cut-off values to discriminate between Down syndrome and normal fetuses was assessed by Fisher's exact test. RESULTS: The mean ratio of measured to expected femur length was significantly lower in the Down syndrome as compared with control population (0.9473, DS 0.0795) versus 1.0, DS 0.0745) (p < 0.0045). The ratio of 0.91 or less predicted Down's syndrome with a sensitivity of 43.7% and a false-positive rate of 8.6%. For women with risk of one in 250 and one in 1000 of having an affected fetus based on maternal age, a shortened femur yielded positive predictive values of one in 26 and one in 105, respectively. CONCLUSION: These results suggest that the sonographic measurement of fetal femur length for the screening of Down syndrome in the low-risk population is hindered by a high false positive rate (about 9%). It follows that the percentage of women requiring an amniocentesis would increase to un unacceptably high level. The utilization of this biometric marker may be helpful, in our opinion, for identifying fetuses at risk for Down syndrome in women between 35 and 38 years of age. These women in fact, are not offered amniocentesis for the prenatal diagnosis of Down's syndrome in the majority of italian institutions. The sonographic measurement of fetal femur length could detect about 45% of fetal Down's syndrome, offering an amniocentesis to 9% of women, with a consequent reduction of the cost required. Only a prospective study can evaluate the efficacy of this method to predict Down syndrome in such group of women.

Adult↗

[Measuring temporal transmission properties of the visual system. Diagnostic value in suspected optic nerve neuritis].

The temporal transfer properties of the visual system were examined in 157 patients with suspected acute optic neuritis or papillitis. Foveal modulation sensitivity was measured as a function of temporal frequency (DeLange curve) both for the affected eye and the unaffected fellow eye. Patients with acute optic neuritis typically show a reduction of foveal modulation sensitivity at all temporal frequencies, high temporal frequencies above 10 cps being more markedly affected. The aim of the present study was to determine the sensitivity and specificity of this simple psychophysical procedure for the diagnosis of neuritis or papillitis in a reasonably large population of patients with suspected acute optic neuritis or papillitis. In each case the final diagnosis was confirmed by evaluation of the clinical signs and symptoms, the course of disease and additional diagnostic procedures, e.g. electrophysiology, perimetry, neurological examination including CT, lumbal puncture and examination of cerebrospinal fluid. In 136 cases (86.6%) the result read from the DeLange curve was correctly positive or negative. In 17 cases (10.8%) the DeLange curve indicated a false-positive and in 4 cases (2.6%), a false-negative result.

Flicker Fusion↗

Strategies for screening blood for human immunodeficiency virus antibody. Use of a decision support system.

A decision analytic model was used to examine alternative strategies to screen donated blood for human immunodeficiency virus (HIV) using data from the literature and from 1987 blood-screening programs in areas with high and low prevalence of HIV. Sensitivity analyses incorporated uncertainties about HIV infection and test performance. Current screening strategies are estimated to allow 20.5 infected units per million donated units to be transfused at a cost of $16,850 per HIV-positive unit detected in high-prevalence areas and 4.7 infected units per million donated units to be transfused at a cost of $32,275 per HIV-positive unit detected in low prevalence areas, with nine false-positive notifications of uninfected patients per million units screened and 14.9 discarded, noninfected units per HIV-positive unit in low-prevalence areas. Testing donated blood for HIV can be improved by individualizing screening strategies for areas with different prevalences of HIV. Efforts to further reduce transfusion-associated HIV should focus on improved test performance in early stages of infection, reduction of unnecessary transfusions, donor recruitment in lower-risk groups, and public health measures to reduce HIV infection among the general population.

Blood Donors↗

Scintigraphic, electrocardiographic, and enzymatic diagnosis of perioperative myocardial infarction in patients undergoing myocardial revascularization.

To assess the incidence of perioperative myocardial infarction, 214 consecutive patients were evaluated 1-5 days after coronary bypass surgery, using Tc-99m pyrophosphate (TcPPi) myocardial imaging, serial electrocardiograms (ECG), and enzyme levels (SGOT, LDH, CPK). On the basis of the clinical course and scintigraphic, enzymatic, and ECG changes, the diagnosis of perioperative infarction was definite in 17 of 241 cases (7.9%) and probable in six of 241 (2.8%). In all of these 23 patients, TcPPi scans were abnormal; one additional patient had a false-positive scintigram. Only 13 of the 23 had ECG evidence of infarction, but there were no false positives. We set the threshold for abnormality of enzyme changes quite high, owing to experience in more than 900 postoperative patients (SGOT greater than 200, LDH greater than 500, CPK greater than 500 on the same day). Using these criteria, 22 of the 23 infarct patients had abnormal enzymes, and six others were falsely positive. These results indicate a relatively low sensitivity for the ECG in diagnosing perioperative infarction, but the lack of false positives suggests high specificity. The sensitivity and specificity of the enzymes and the TcPPi image were both excellent and quite similar; the main difference was a reduction of certainty of infarction with the enzyme criteria, caused by the six patients whose enzyme values were falsely positive. Considering its sensitivity, specificity, and ability to locate and to a certain extent quantitate necrosis. TcPPi imaging is probably the most valuable means of diagnosing perioperative myocardial infarction.

Clinical Enzyme Tests↗