Detection of an antigen containing 3-hydroxyanthranilic acid in the sera of patients with tumors of different localizations]

An unusual antigen containing a carcinogenic tryptophane metabolite -- 3-hydroxyanthranylic acid as a hapten (3-HAA-antigen) was found to be present in the blood serum in the overwhelming majority of patients with malignant tumours of various stages and localizations. The 3-HAA-antigen was rarely determined in the patients with nonmalignant diseases was not revealed in the blood serum of healthy donors and patients with benign tumours. The significance of the data obtained for the diagnosis of the tumour process, irrespective of its localization, is discussed.     

血清半乳甘露聚糖检测对血液病患者侵袭性曲霉菌感染早期诊断的价值

目的 评价血清半乳甘露聚糖(GM)检测对血液病患者侵袭性曲霉菌(IA)感染早期诊断的价值.方法 前瞻性采用酶联免疫吸附试验(ELISA)每周2次测定患者的GM水平,并计算该诊断试验的各项评价指标.结果 共有来自92例患者的113例次感染进入研究,检测血清标本472份,以确诊IA感染和临床诊断IA感染为真阳性组,排除IA感染为真阴性组,0.7为阈值,连续2次GM结果阳性为真阳性,该诊断试验的敏感度为83.3%,特异度为91.1%,阳性预测值为78.9%,阴性预测值为93.1%.GM阳性结果较痰培养阳性时间提前4 d(1～7 d),比影像学改变提早7 d(1～14 d),较抗真菌治疗提前6 d(1～15 d).结论 通过ELISA方法进行血清GM检测可以快速、灵敏的为早期诊断IA感染提供有力证据.     

Detection of proliferating cell nuclear antigen (PCNA) in peripheral blood mononuclear cells and sera of patients with malignant lymphoma

The proximity of farms to badger setts was compared between farms that had experienced a tuberculosis breakdown and those that had not, over the 6 year period from 1988 to 1993. The data were derived from a badger removal study conducted in East Offaly County in the Republic of Ireland. Badger removal began in 1989 and continued through 1993; by the end of 1990, approximately 80% of all badgers caught in the 6 year period had been removed. All badgers were examined, grossly, for evidence of tuberculosis. Tuberculosis status of the approximately 900 study herds was based on the results of the single intradermal comparative skin test and/or lesions of bovine tuberculosis. All herds were tested at least once annually. The number of herds experiencing bovine tuberculosis declined over the period, particularly in the years 1992 and 1993. The data on farm and badger sett location were stored and analysed, initially, in a geographical information system. Owing to the badger removal programme, the distance between the barn yard of a typical farm and the nearest occupied badger sett increased, by about 300 m year-1, and by about 600 m year-1 to the closest infected sett. In bivariate analyses, in the years 1988 and 1989, the risk of tuberculosis declined with increasing distance to a badger sett containing one or more tuberculous badgers. In multivariable logistic regression analyses, year and the average number of cattle tested per farm per year were controlled. A second identical analysis was conducted to control for the repeated observations on the same herds using generalised estimating equations. In both analyses, the risk of a multiple reactor tuberculosis breakdown decreased for herds at least 1000 m away from an infected badger sett, and increased as the number of infected badgers per infected sett increased. Despite the significantly reduced risk of a breakdown with increasing distance to infected badger setts, the relationship was not strong (sensitivity and specificity of the model in the low 70% range) and explained only 9-19% of tuberculosis breakdowns.     

Evaluation of PCR for detection of DNA specific for Aspergillus species in sera of patients with various forms of pulmonary aspergillosis

Pulmonary aspergillosis is classified into invasive, saprophytic, and allergic forms. In this study, we evaluated the usefulness of PCR for differentiating between different forms of aspergillosis or in monitoring disease activity during treatment by detecting DNA specific for Aspergillus species in the serum. Nested PCR was used to detect Aspergillus DNA in the sera of 30 patients with various forms of pulmonary aspergillosis. The results were compared with those of latex agglutination tests for detecting galactomannan antigen. We also examined the serial changes in the results of nested PCR during and after treatment of a subgroup of patients with invasive pulmonary aspergillosis with amphotericin B. The highest proportion of positive nested PCR results were in patients with invasive aspergillosis (10 of 12; 83%), while patients with pulmonary aspergilloma had the lowest frequency of positive tests (1 of 9; 11%). These results suggested that the sensitivity of the nested PCR depends on the extent of invasion by Aspergillus species. Serial assays showed that the results of nested PCR became negative shortly after commencement of antifungal treatment and that such changes did not correlate with clinical responsiveness to treatment. Our results indicate the potential usefulness of nested PCR with serum samples for the diagnosis of invasive aspergillosis and the detection of a shift in the status of infection from a noninvasive type to invasive aspergillosis. However, the results of the nested PCR did not correlate with the response to antifungal treatment.     

The sentinel node biopsy in patients with breast cancer: recommendations for the introduction of this procedure. Dutch Working Group Sentinel Node Biopsy in Breast Cancer

Sentinel node biopsy may be useful in the staging of breast cancer. In experienced hands presence or absence of metastasis in the sentinel node accurately predicts the nodal status and in patients with a negative sentinel node biopsy axillary dissection may be avoided. The technique, however, shows a clear learning curve and hasty introduction may lead to an unacceptable rate of false negative biopsies. Moreover, the introduction of the technique in general practice should be well coordinated in order to prevent large differences between hospitals in the staging and treatment of breast cancer patients. On the initiative of NABON (Nationaal Borstkanker Overleg Nederland; 'national breast cancer consultation') and the Nederlandse Vereniging voor Chirurgische Oncologie (Netherlands Association for Surgical Oncology) a study group was formed to co-ordinate the introduction of the sentinel node biopsy in breast cancer patients in the Netherlands. Important topics are central registration of all procedures in order to evaluate its applicability and technical variations, the performance in each centre of at least 50 procedures together with axillary node dissection to evaluate the results before clinical application is considered, and nationwide co-ordination to find the best therapy for patients with positive sentinel nodes.     

Detection of isotype-specific autoantibodies to calpastatin in sera from patients with rheumatic diseases using heat-treated HeLa cell extract as an antigen source for immunoblotting

To detect immunoglobulin isotype-specific autoantibodies to native human calpastatin in patients with rheumatic diseases, we performed immunoblot analysis using the heated HeLa cell extracts to enrich heat-resistant calpastatin. The calpastatin molecule that was apparently migrated to 110 kD by SDS-PAGE was confirmed to react with monoclonal anti-human calpastatin antibody in immunoblotting. IgG antibodies to calpastatin were detected in 22 of 48 sera (46%) from patients with RA, whereas only 20% (5/25), 11% (2/19) and 13% (2/15) of sera from SLE, SSc and PM/DM had IgG anti-calpastatin antibodies, respectively. IgM antibodies were also found in 40% (19/48) of RA and 12% (3/25) of SLE patients but not detected in sera from patients with other rheumatic diseases. IgA antibodies were found in only one RA and one SLE serum. In RA, 7 of 48 sera (15%) had IgM antibodies alone, but all SLE sera with IgM antibodies had IgG antibodies. Thus, anti-calpastatin autoantibodies were detected by using the native human calpastatin. Although these autoantibodies were found in patients with various rheumatic diseases, they were present in RA patients at the highest frequency. In particular, the presence of IgM antibodies appeared to be more specific in RA patients.     

Carcinoembryonic antigen in patients treated with radiation therapy for invasive squamous cell carcinoma of the uterine cervix

Plasma carcinoembryonic antigen (CEA) levels in 75 patients with invasive cervical cancer were measured during and after radiation therapy. Initial CEA levels were elevated in 65% of the patients, the incidence varying with stage of disease. Of the 32 patients followed during therapy, CEA levels rose in 26 (81%). CEA values after therapy in the same 32 patients showed three patterns: (1) decline to normal, associated with a disease-free state; (2) decline but not to normal, associated with heavy cigarette smoking or persistent disease; and (3) decline to normal, followed by a rise to abnormal, associated with tumor recurrence. Elevation of CEA levels preceded recognition of recurrent cervical cancer by as much as 4 months in five of seven patients.     

Presence of IgM antibodies to Trypanosoma cruzi urinary antigen in sera from patients with acute Chagas'' disease

We have investigated the ability of an antisense immunoglobulin E (IgE) receptor alpha-subunit oligodeoxynucleotide (Fc epsilon RI alpha ODN) specifically to inhibit IgE-mediated allergic reactions in the mouse. Synthetic antisense Fc epsilon RI alpha ODN dose-dependently inhibited passive cutaneous anaphylaxis and histamine release from the mouse peritoneal mast cells (MPMC) activated by anti-dinitrophenyl (DNP) IgE. Northern blot analysis showed that the mast cells treated with antisense Fc epsilon RI alpha ODN exhibited no detectable levels of L-histidine decarboxylase mRNA after anti-DNP IgE stimulation, whereas the cells treated with sense Fc epsilon RI alpha ODN possessed significant amounts of this mRNA. Examination of the elevation of cAMP levels in MPMC following the activation with anti-DNP IgE demonstrated a significant rise in activated cells, but not in the antisense Fc epsilon RI alpha ODN-treated cells. Moreover, antisense Fc epsilon RI alpha ODN had a significant inhibitory effect on anti-DNP IgE-induced tumour necrosis factor-alpha production. Our results demonstrated that antisense Fc epsilon RI alpha ODN inhibited the IgE-mediated allergic reaction in vivo and in vitro.     

Detection of Salmonella in dry foods using refrigerated pre-enrichment and enrichment broth cultures: interlaboratory study

An interlaboratory study was performed in 11 laboratories to validate the use of pre-enrichment and tetrathionate brilliant green (TBG35) and selenite cystine (SC35) enrichment cultures refrigerated 72 h at 2-5 degrees C for greater analytical flexibility in the detection of Salmonella in dry foods. Productivities of refrigerated pre-enrichment and enrichment cultures were compared with that of the AOAC/Bacteriological Analytical Manual (BAM) procedure using 4 food types: whole egg powder, milk chocolate, animal feed, and instantized skim milk powder. Uninoculated and inoculated samples were included in each food group. There was complete agreement between the results obtained by the standard AOAC/BAM procedure and the 2 refrigeration procedures. Of 660 samples tested, the AOAC/BAM procedure identified 393 contaminated samples that were readily detected from the corresponding refrigerated pre-enrichment cultures and from the combined productivity of homologous refrigerated TBG35 and SC35 cultures. Refrigeration (72 h) of pre-enrichment or enrichment cultures for greater analytical flexibility and laboratory productivity in the examination of dry foods is under review for adoption by AOAC International.     

Detection of gluten in human sera by an enzyme immunoassay: comparison of dermatitis herpetiformis and celiac disease patients with normal controls

We have developed a triple sandwich enzyme immunoassay to detect circulating gluten in human sera. With human sera containing known amounts of added gluten as controls, the assay was sensitive in the range of 0.75 to 75 micrograms of gluten per ml of serum. Forty-one control subjects were compared to 21 patients with dermatitis herpetiformis and 11 patients with celiac disease. The dermatitis herpetiformis and celiac disease patients had significant elevation of serum gluten values over the control subjects. Circulating gluten antigenemia is a previously unrecognized feature which may be important in understanding the pathogenesis of dermatitis herpetiformis and celiac disease.     

Carbohydrate antigen 195 (CA 195) in the sera of patients with esophageal, hepatic and biliary tract carcinomas

In this work the problems of obtaining medicinal forms of lactobacterin with the use of nontraditional methods for the stabilization of biomass are considered. The data on the stability of tablets, suppositories and microgranules of the preparation prepared on the basis of immobilized cells, are presented.     

Reliability and accuracy in reporting CIN in 14 laboratories. Developing new indices of diagnostic variability in an interlaboratory study. The Working Group for External Quality Control in Cervical Cytopathology

OBJECTIVE: To report the results of the second phase of a pilot study of an Italian national external quality evaluation program (EQA) aimed at assessing whether participation in the first phase had increased the reliability and accuracy of diagnoses and to what extent. STUDY DESIGN: In the second phase, two sets of cervical smears (similar to the ones examined in the first phase) were circulated among the 14 participating cytologic laboratories throughout Italy. Responses were recorded on a standardized form. Participants were asked to judge the adequacy of each smear and to formulate a diagnosis. They were also asked to recommend management of the patient on the basis of the smear report and to evaluate the degree of diagnostic difficulty of each slide. The results were discussed in workshops, and it was possible to reach a consensus diagnosis on 37 of 40 smears. In the statistical analysis, new indices of diagnostic variability were developed and calculated; a gross index of agreement, unweighted and weighted kappas, analysis of exchangeability, sensitivity and specificity were also estimated. RESULTS: The results of the second phase are similar to those of the first phase and no substantial improvement in accuracy and little reduction in variability were observed. The interventions carried out in this study (discussion between representatives of laboratories of diagnostic differences and reassessment of the most controversial slides) were aimed at increasing consensus among the participating pathologists but were insufficient to change the diagnostic routines in their laboratories. CONCLUSION: It may be advisable to promote two kinds of interlaboratory quality programs with two separate but integrated components: (1) a core component with slides having clear-cut diagnoses, and (2) a continuing education component.     

Detection of antibodies to Candida albicans germ tubes for diagnosis and therapeutic monitoring of invasive candidiasis in patients with hematologic malignancies

We prospectively investigated the ability of detection of antibodies to Candida albicans germ tubes (CAGT) to diagnose invasive candidiasis in 95 consecutive admissions of 73 patients with hematologic disorders undergoing intensive chemotherapy. The episodes were divided into three groups according to clinical and microbiological diagnosis. Group 1 comprised eight admissions of eight patients with invasive candidiasis. Group 2 comprised 42 admissions of 34 patients without evidence of invasive candidiasis. Group 3 comprised the remaining 45 admissions of 37 patients with febrile episodes which were not diagnosed by microbiological culture. Antibodies to CAGT were detected in 87.5% of group 1 patients. Detection of antibodies to CAGT in patients with Candida fungemia was delayed somewhat relative to the time the blood culture was positive, but antibodies to CAGT were detected earlier than a diagnosis was made in patients with deep-tissue candidiasis. Sera from 2 admissions in group 2 and 12 admissions in group 3 revealed antibodies to CAGT. At a titer of > or = 1:20, detection of antibodies to CAGT had a sensitivity of 87.5%, specificity of 95.2%, positive predictive value of 77.8%, and negative predictive value of 97.6%. Antibodies to CAGT were usually detected before beginning of empiric antifungal therapy. Titers of antibodies to CAGT were maintained in most patients who died but declined and eventually disappeared in the patients who survived. Since antibodies to CAGT were detected in all patients with tissue-proven invasive candidiasis but negative by blood culture, detection of antibodies to CAGT complemented blood cultures for diagnosis and therapeutic monitoring of patients with hematologic malignancies and invasive candidiasis.     

Risk assessment for patients with chronic myeloid leukaemia before allogeneic blood or marrow transplantation. Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation

BACKGROUND: Transplantation of blood or bone-marrow stem cells is the treatment of choice for selected patients with chronic myeloid leukaemia (CML). Transplantation is used with increasing frequency and success, but remains associated with substantial risks of morbidity and mortality. Other treatments with satisfactory short-term outcome are available. For appropriate counselling of patients, a rapid and simple way to assess risk is needed. METHODS: Data from 3142 patients (1873 [60%] male, 1269 [40%] female; mean age 34 years, range <1-60 years) treated with allogeneic blood or marrow transplants for CML between 1989 and 1997, reported to the European Group for Blood and Marrow Transplantation (EBMT), were used to develop and test a simple risk score based on previously reported major pretransplant risk factors: histocompatibility, stage of disease at time of transplantation, age and sex of donor and recipient, and time from diagnosis to transplantation. We analysed probabilities of survival, leukaemia-free survival, transplant-related mortality, and relapse incidence with respect to these risk factors. FINDINGS: At the time of analysis, 1922 (61%) of the 3142 patients were alive-1567 (65%) of those with HLA-identical sibling donors and 417 (57%) of those with unrelated donors. 1682 (54%) were alive without relapse. 1220 (39%) patients had died, 1013 (83%) of transplant-related causes, 207 (17%) of relapse. 447 (14%) patients had relapsed. The final scoring system was highly predictive for leukaemia-free survival, survival and transplant-related mortality. Survival at 5 years was 72%, 70%, 62%, 48%, 40%, 18%, and 22% for patients with scores 0, 1, 2, 3, 4, 5, and 6, respectively. Risk of transplant-related mortality was 20%, 23%, 31%, 46%, 51%, 71%, and 73%. Data showed the same trends for HLA-identical sibling transplants and unrelated transplants for transplants done in 1989-93 and 1994-96. INTERPRETATION: Pretransplant risk factors are cumulative for individual patients with CML having blood or marrow transplantation. A simple system based on five main factors gives adequate risk assessment for counselling of patients and taking decisions.     

Postchemotherapy residual masses in germ cell tumor patients: content, clinical features, and prognosis. Medical Research Council Testicular Tumour Working Party

BACKGROUND: In a retrospective study that included a detailed histopathologic review, the clinicopathologic features of patients with germ cell tumors (GCT) and resectable residual masses after chemotherapy were assessed. METHODS: Histologic material from 153 patients was available for review. Recorded details included primary histologic diagnosis, location, size and number of metastases, marker levels before and after chemotherapy, and completeness of surgical excision. A median of seven histologic sections per resection were reviewed by two pathologists independently (and together when disagreement occurred). In each case, details were recorded regarding fibrosis, necrosis, hemorrhage, embryonal carcinoma (undifferentiated teratoma), yolk sac tumor, choriocarcinoma (trophoblastic tumor), differentiated teratoma (mature and immature), dysplasia in somatic tissues, and non- germ cell tumor (GCT) malignancies. The percentage of the sample that each of these components comprised was also estimated. RESULTS: The median postchemotherapy follow-up time was 7 years, and 38 of 153 patients (25%) experienced disease progression. In a multivariate analysis, incomplete resection of all residual masses (in 38 patients) and the presence of malignant elements (in 23 patients) were independent risk factors for progression. In the subset of patients in whom all masses were completely resected, the presence of embryonal carcinoma (undifferentiated teratoma) was the single most significant risk factor for progression. Seven percent of patients had this factor, which was associated with a 2-year progression free survival rate of 12.5%, compared with 88.0% where this component was absent. CONCLUSIONS: Progression free survival can be predicted well by the completeness of excision of residual masses and the presence of malignant germ cell elements. The latter confers a relatively poor prognosis even if all of these elements are completely resected.