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Modified nucleosides: an accurate tumour marker for clinical diagnosis of cancer, early detection and therapy control.

Modified nucleosides, regarded as indicators for the whole-body turnover of RNAs, are excreted in abnormal amounts in the urine of patients with malignancies. To test their usefulness as tumour markers and to compare them with the conventional tumour markers, fractionated urine samples were analysed using chromatography. The excretion patterns of nucleosides of 68 cancer patients with malignant and benign tumours and 41 healthy controls have been studied. Significant elevations in the total sum and the concentrations of at least three (or four) of indicator nucleosides cytidine, pseudouridine, 2-pyridone-5-carboxamide-N1-ribofuranoside, N2,N2-dimethylguanine, 1-methylguanosine, 2-methylguanosine and 1-methyladenosine indicate a tumour with a sensitivity of 54% (77%) and a specificity of 86% (98%). Using an artificial neural network analysis, a sensitivity of 97% and a specificity of 85% were achieved in differentiating between tumour and control volunteers. The comparison with carcinoembryonic antigen, cancer antigen 15-3 und tissue polypeptide antigen indicates that urinary nucleosides may be useful tumour markers. This study suggests that the simultaneous determination of modified nucleosides and creatinine in urine samples of patients with cancer leads to an advantage to current methods and is a useful method to detect cancer early and to control the success of therapy.

Adult↗

[Clinical relevance of the early detection of arthrosis].

In the years 1989 to 1992 615 local persons underwent yearly examinations for analysis of osteoarthrosis of the hip and knee by means of comprehensive documentation of orthopaedic health history and clinical findings. Of special interest in our investigation were the Altman ACR criteria for osteoarthrosis of the hip and knee over the years. We can show, that finding the diagnosis is as accurate with the ACR criteria as well as the far more extensive Lequesne and Tegner-Lysholm score. Analysis of the investigations over the years revealed clearly different results in the frequency of osteoarthrosis. The reason is the nature of osteoarthrosis changing between silent and active phases especially during time of onset. Our investigations show, that valuable criteria exists for detection of early osteoarthrosis, however apparent are deficits for observing its course.

Adult↗

Comparison of in situ hybridization and monoclonal antibodies for early detection of cytomegalovirus in cell culture.

The abilities of each of four diagnostic tests--direct fluorescent monoclonal antibody (direct FA) staining, indirect fluorescent monoclonal antibody (indirect FA) staining, in situ hybridization with biotinylated DNA probes, and in situ hybridization with DNA probes directly linked to enzymatically active horseradish peroxidase-to detect cytomegalovirus soon after culture were compared. Only the indirect FA test and the in situ hybridization method with directly linked HRP-DNA probes provided consistent and reliable cytomegalovirus detection as early as 15 h postinfection.

Antibodies, Monoclonal↗

Usefulness of the direct agglutination test in the early detection of subclinical Leishmania donovani infection: a community-based study.

The value of a direct agglutination test (DAT) in the detection of subclinical infections with Leishmania donovani has recently been investigated in the Indian state of Bihar, after the sensitivity and specificity of the test had been determined. When used to screen sera from 108 parasitologically confirmed cases of visceral leishmaniasis, 50 patients with active, non-leishmanial infection, and 641 healthy controls living close to, or distant from, an endemic area, the test was found to be 91.7% sensitive and 100% specific if a titre of 1:800 was used as the threshold for seropositivity. During a longitudinal clinical study in a rural, VL-endemic area of the Indian state of Bihar, the test was used, with 1:800 set as the threshold titre, to determine the baseline prevalence of infection with L. donovani among villagers who, though showing no symptoms of VL, had recently been febrile for at least 2 weeks. The 234 subjects of this study were either VL-case contacts [i.e. members of households in which there were active or cured VL cases (N=78)] or the members of control households with no cases or history of the disease (N=156). The results of DAT at the start of the study indicated that 49 (20.9%) of the subjects--29 (37.2%) of the VL-case contacts and 20 (12.8%) of the other subjects--were seropositive and therefore probably had subclinical infections with L. donovani. During the subsequent 9 months of follow-up, however, only eight of the subjects found seropositive at the start of the study--seven (24.1%) of the seropositive case contacts but only one (5.0%) of the other seropositives--developed symptomatic VL, all by month 6 of the follow-up. Compared with their neighbours, therefore, individuals who shared households with active or cured cases of VL appeared at greater risk not only of L. donovani infection (indicating focal transmission) but also of developing symptomatic disease once infected. Curiously, among the seropositive case contacts, those from the households that harboured active cases of VL at the baseline survey were less likely to develop symptomatic VL during the 9 months of follow-up than those from households that harboured only cured cases (18.8% v. 30.8%). The wide-spread use of DAT could allow the detection and early treatment of latent L. donovani infections and so contribute to the elimination of VL, at least as a public-health problem, from India.

Agglutination Tests↗

Early detection of response to radiation therapy in patients with brain malignancies using conventional and high b-value diffusion-weighted magnetic resonance imaging.

PURPOSE: To study the feasibility of using diffusion-weighted magnetic resonance imaging (DWMRI), which is sensitive to the diffusion of water molecules in tissues, for detection of early tumor response to radiation therapy; and to evaluate the additional information obtained from high DWMRI, which is more sensitive to low-mobility water molecules (such as intracellular or bound water), in increasing the sensitivity to response. PATIENTS AND METHODS: Standard MRI and DWMRI were acquired before and at regular intervals after initiating radiation therapy for 10 malignant brain lesions in eight patients. RESULTS: One week posttherapy, three of six responding lesions showed an increase in the conventional DWMRI parameters. Another three responding lesions showed no change. Four nonresponding lesions showed a decrease or no change. The early change in the diffusion parameters was enhanced by using high DWMRI. When high DWMRI was used, all responding lesions showed increase in the diffusion parameter and all nonresponding lesions showed no change or decrease. Response was determined by standard MRI 7 weeks posttherapy. The changes in the diffusion parameters measured 1 week after initiating treatment were correlated with later tumor response or no response (P <.006). This correlation was increased to P <.0006 when high DWMRI was used. CONCLUSION: The significant correlation between changes in diffusion parameters 1 week after initiating treatment and later tumor response or no response suggests the feasibility of using DWMRI for early, noninvasive prediction of tumor response. The ability to predict response may enable early termination of treatment in nonresponding patients, prevent additional toxicity, and allow for early changes in treatment.

Brain↗

Early detection of secretogranin-II (SgII) in the human fetal pituitary: immunocytochemical study using an antiserum raised against a human recombinant SgII.

Secretogranin-II (SgII) is a protein contained within secretory granules of mainly gonadotrophs. The purpose of this study was to determine whether SgII immunoreactivity (SgII-IR) in the human fetal pituitary was temporally related to gonadotropin immunoreactivity. A specific antihuman SgII antiserum was thus required. A complementary DNA clone with an open reading frame for human (h) SgII was synthesized by reverse transcription-polymerase chain reaction from pituitary total RNA. This clone was used to obtain the SgII polypeptide (-9 to 152) as a fusion protein, in a heterologous expression prokaryotic system. Antisera against the fusion protein were raised in rabbits and checked for specificity and sensitivity through Western blotting. Human fetal pituitaries from week 6 of gestation onward were used for immunocytochemical studies. Consecutive semithin sections were treated with the specific antisera against hSgII, beta-endorphin, and hPRL and with monoclonal antibodies to hCG alpha, hLH, and hFSH. SgII immunoreactivity appeared at week 8 and was restricted to pituitary cells expressing beta-endorphin (100% colocalization). At week 9, FSH-positive cells did not contain SgII. From week 10, gonadotrophs progressively exhibited SgII-IR, up to 50% of that in FSH-containing cells at week 26. The granin was never found in PRL cells whatever the stage of development. The present data demonstrate that SgII-IR is detected very early in fetal life; however, the positive cells are not gonadotrophs, but corticotrophs. Within gonadotrophs, SgII appears subsequent to hormones. At birth, more than 90% of SgII-IR cells are represented by corticotrophs and gonadotrophs.

Adrenal Glands↗

Early detection of doxorubicin-induced myocardial damage by ultrasound tissue characterization with integrated backscatter.

Doxorubicin (DXR) is one of the most effective antineoplastic agents, but its use is limited by its myocardial toxicity. Myocardial injury reduces the cyclic variation of integrated backscatter (CV-IBS) and so the present study was designed to investigate whether CV-IBS can be used to detect the early phase of myocardial damage in patients receiving DXR. Thirty-four subjects constituted the study population, none of whom showed clinically evident heart failure. CV-IBS was obtained for both the interventricular septum and the left ventricular posterior wall in the parasternal short-axis view. Standard echographic measures of left ventricular function were also made. Subjects without DXR exposure or evident cardiac diseases served as controls. The total dose of DXR administered per patient was 339+/-164 mg/m2 (range: 95-680 mg/m2). Conventional echographic parameters, including left ventricular wall thickness, dimensions, fractional shortening, and ejection fraction, showed no significant differences between the 2 groups. In contrast, CV-IBS was significantly decreased in the DXR group compared with the control group (septum: 4.7+/-1.7 vs 7.2+/-1.9 dB, p<0.0001; posterior wall: 6.7 +/-2.2 vs 8.0+/-1.6 dB, p<0.05). CV-IBS can be used as an early indicator of DXR-induced myocardial damage in patients demonstrating normal left ventricular systolic function.

Adult↗

Early detection of sacroiliitis on magnetic resonance imaging and subsequent development of sacroiliitis on plain radiography. A prospective, longitudinal study.

OBJECTIVE: To investigate the diagnostic value of magnetic resonance imaging (MRI) in the detection of early sacroiliitis. METHODS: Twenty-five consecutive HLA-B27 positive patients with inflammatory low back pain and < or = grade 2 unilateral sacroiliitis on conventional radiography (modified New York criteria) were studied. Erythrocyte sedimentation rate, C-reactive protein, plain radiography (PR), and MRI of the sacroiliac (SI) joints were obtained at study entry and PR of the SI joints after 3 years. Each radiograph and MR image set was interpreted independently. SI joints were scored according to the modified New York Criteria for radiological sacroiliitis. MRI scans were also scored for the presence of subchondral marrow edema. The relationship between > or = grade 2 sacroiliitis (by modified New York criteria for radiological sacroiliitis) shown on MRI and the subsequent development of > or = grade 2 sacroiliitis on PR after 3 years was investigated. RESULTS: At study entry > or = grade 2 sacroiliitis was found on MRI in 36 of 50 SI joints. Edema was found in 20 of 50 SI joints. After 3 years > or = grade 2 sacroiliitis was found on PR in 21 of 44 SI joints. The positive predictive value of > or = grade 2 sacroiliitis on MRI for the development of > or = grade 2 sacroiliitis on PR after 3 years was 60%; sensitivity was 85% and specificity 47%. CONCLUSION: Our data suggest that MRI of the SI joints can be used to identify sacroiliitis earlier than PR.

Adult↗

[Early detection of scleroderma in quartz dust exposed workers and workers with silicosis by determining serum beta-galactosidase activity].

Progressive systemic sclerosis (PSS) is a rare disease belonging to the collagen diseases. PSS is frequently observed in workers with an intensive exposure to crystalline silica and with silicosis in the GDR. The recognition as an occupational disease is regulated by law. The elevated beta-galactosidase activity in the serum of patients with silicosis and beginning PSS can be used for detecting of early stages of PSS. References are given to medical care of patients with silicosis and exposure to quartz.

Adolescent↗

Early detection of skeletal muscle injury by assay of creatine kinase MM isoforms in serum after acute exercise.

We could detect skeletal muscle injury early after an acute exercise bout by measuring creatine kinase (CK, EC 2.7.3.2) MM isoforms in serum. Eleven men performed 120 alternating-arm, eccentric (muscle lengthening) biceps contractions with the intensity of each contraction being 110% of maximal concentric strength--a form of exercise previously shown to cause significant increases of CK in serum at 24 h and muscle soreness 48 h after exercise. Total CK and CK-MM isoform activities in serum were determined before and at 0.5, 0.75, 1, 1.5, 2, and 6 h after exercise. Using thin-film agarose gels and a rapid isoelectric focusing technique, we separated the MM isoforms into MM3 (skeletal muscle form), MM2, and MM1 (in vivo conversion forms). The isoforms reflected the MM form released into the serum from tissue as well as the conversion of one form to another. There were no significant increases in total CK from before to 6 h after exercise: 75 (SD 36) vs 91 (SD 33) U/L. However, CK MM3 in serum increased significantly (P less than 0.01) within 2 h after exercise from 22 (SD 6)% to 28 (SD 6)%. The MM3 to MM1 ratio also increased significantly (P less than 0.05) during this time, from 0.6 (SD 0.3) to 0.9 (SD 0.4). Thus, quantification of CK MM isoforms permitted very early detection of skeletal muscle enzyme release.

Creatine Kinase↗

Predictive value of the Bayley mental scale in the early detection of cognitive delays in high-risk infants.

One of the most elusive developmental disabilities to diagnose during infancy is cognitive delay. Although infant intelligence tests have been identified repeatedly as poor predictors of future IQ, these predictions have typically been based on interage correlations. This retrospective study examined the sensitivity, specificity, and positive and negative predictive values of the Mental Scale of the Bayley Scales of Infant Development in detecting cognitive delay (IQ < 85) among a sample of 196 high-risk, mostly low birth weight, premature infants who were assessed initially at 4 months' corrected age and followed longitudinally to between 3 and 8 years' corrected age. As hypothesized, the Bayley Mental Scale was better at correctly identifying children with future normal IQs (specificity = 91.9%) than it was at identifying infants who would later show cognitive delays (sensitivity = 38.9%). The positive and negative predictive values were 51.9% and 87.0% respectively. Results of this study support recent assertions that cognitive delay, particularly in the mildest forms, is difficult to detect during early infancy.

Cognition Disorders↗

Early detection and identification of Trichophyton verrucosum.

A new medium for the early detection and identification of Trichophyton verrucosum has been formulated. The key ingredients of the medium are 4% casein and 0.5% yeast extract. T. verrucosum is recognized by its early hydrolysis of casein and very slow growth. Microconidia were produced by 19 out of 35 isolates (54%), and macroconidia were produced by 8 out of 35 isolates (23%). All isolates formed chains of chlamydospores at 37 degrees C, and 24 out of 35 isolates formed chains at 28 degrees C. Nutritional requirements of all 35 strains of T. verrucosum were confirmed. The medium was evaluated by isolating 570 suspected T. verrucosum from skin scrapings. The early detection of hydrolysis, formation of characteristic chains of chlamydospores, and restricted slow growth of this dermatophyte differentiate it from T. schoenleinii.

Caseins↗

Early detection of deafness in young children.

It is generally accepted that early detection and intervention for children with hearing defects, either congenital or acquired, is both necessary and advantageous. Detection before the end of the first year of life seems to improve speech acquisition, lessen the likelihood of behaviour problems and decrease the cost of education. The methods for early detection are discussed and a procedure is recommended.

Acoustic Stimulation↗

Early detection of first-episode psychosis: the effect on 1-year outcome.

UNLABELLED: Early intervention is assumed to improve outcome in first-episode psychosis, but this has not been proven. OBJECTIVE: To study whether 1-year outcome will be better in a health care sector with early detection (ED) of psychosis compared with sectors with no early detection (no-ED). DESIGN: A quasi-experimental study with ED in 2 experimental sectors and no-ED in 2 control sectors. ED was achieved through low-threshold ED teams and information campaigns about psychosis for the public, schools, and primary health care providers. The ED and no-ED health care areas offered an equivalent assessment and treatment program during the first year. Two hundred and eighty-one patients were included; 88% were reassessed after 1 year. RESULTS: The ED-area patients (N = 141) had a median duration of untreated psychosis of 5 weeks at baseline compared with 16 weeks for patients in the no-ED area (N = 140). Positive and general symptoms, global assessment of functioning, quality of life, time to remission, and course of psychosis at 1 year after the start of treatment were not different between ED and no-ED groups. Outcome was significantly better for the ED area for negative symptoms. CONCLUSIONS: The ED, no-ED differences at baseline become attenuated by 1 year but not the difference in negative symptoms, suggesting secondary prevention in this domain of psychopathology. However, this possibility requires further testing by follow-up and replication.

Adolescent↗