Reduction of false negative results in screening of newborns for homocystinuria.
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BACKGROUND: Mental retardation and other disabilities (including ectopia lentis, osteoporosis, and thromboembolism) in patients who have homocystinuria as a result of a deficiency of cystathionine beta-synthase can be prevented by the screening of newborns with measurement of blood methionine, followed by the early treatment of affected infants. Many infants with this disorder, however, are not identified by screening and have irreversible brain damage. METHODS: We reviewed the results of neonatal screening for homocystinuria over a period of 32 years in New England. Additional specimens were requested for repeated analysis when blood methionine measurements were at or above the established cutoff level. Homocystinuria due to cystathionine beta-synthase deficiency was confirmed by quantitative amino acid analyses. RESULTS: For the first 23.5 years of the review period, the blood methionine cutoff value was 2 mg per deciliter (134 micromol per liter). Among the 2.2 million infants screened during that period, 8 with homocystinuria were identified (1:275,000). In 1990, the cutoff value was reduced to 1 mg per deciliter (67 micromol per liter). Among the 1.1 million infants screened in the subsequent 8.5 years, 7 with the disorder were identified (1:157,000). During the latter period, the specimens were collected from six of the seven infants when they were two days of age or less; five of the six had blood methionine concentrations below 2 mg per deciliter. Use of the reduced cutoff level increased the false positive rate from 0.006 percent to 0.03 percent. CONCLUSIONS: A cutoff level for blood methionine of 1 mg per deciliter in neonatal screening tests for homocystinuria should identify affected infants who have only slightly elevated concentrations of methionine and reduce the frequency of false negative results. (+info)
Melanoma-inhibiting activity (MIA) mRNA is not exclusively transcribed in melanoma cells: low levels of MIA mRNA are present in various cell types and in peripheral blood.
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The detection of minimal amounts of melanoma cells by tyrosinase reverse transcription polymerase chain reaction (RT-PCR) is seriously hampered by false negative reports in blood of melanoma patients with disseminated melanoma. Therefore, additional assays which make use of multiple melanoma markers are needed. It has been shown that introduction of multiple markers increases the sensitivity of detection. Melanoma inhibitory activity (MIA) is one such melanoma-specific candidate gene. To test the specificity of MIA PCR, we performed 30 and 60 cycles of PCR with two different sets of MIA specific primers on 19 melanoma and 16 non-melanoma cell lines. MIA mRNA was detected in 16 out of 19 melanoma cell lines and in seven out of 16 non-melanoma cell lines after 30 cycles of PCR. However, MIA mRNA could be detected in all cell lines after 60 cycles of PCR. Also, in 14 out of 14 blood samples of melanoma patients, five out of six blood samples of non-melanoma patients and in seven out of seven blood samples of healthy volunteers, MIA mRNA was detected after 60 cycles of PCR, whereas no MIA PCR product could be detected in any of the blood samples after 30 cycles of PCR. We conclude that low levels of MIA transcripts are present in various normal and neoplastic cell types. Therefore, MIA is not a suitable marker gene to facilitate the detection of minimal amounts of melanoma cells in blood or in target organs of the metastatic process. (+info)
Efficacy of early diagnosis and treatment in women with a family history of breast cancer. European Familial Breast Cancer Collaborative Group.
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BACKGROUND: Surveillance programmes for women at increased genetic risk of breast cancer are being established worldwide but little is known of their efficacy in early detection of cancers and hence reduction in mortality. METHODS: Data were contributed from seven centres participating in the EU Demonstration Programme on Clinical Services for Familial Breast Cancer. All breast tumours (n = 161) detected prospectively, from the time of enrolment of women in a screening programme, were recorded. Analysis took account of age at diagnosis, whether tumours were screen-detected or not, their pathological stage and outcome by Kaplan-Meier survival plots. RESULTS: Mean age at diagnosis was 48.6 years. Overall, 75% of tumours were detected in the course of planned examinations. For women under age 50 at diagnosis, this figure was 68%. Eighteen percent were mammographically negative, (23% in patients under age 50). At first ("prevalence") round and at follow-up screening, 16% and 22% of tumours respectively were carcinoma in situ (CIS) while 27% and 22% respectively had evidence of nodal or distant spread (CaN+). Comparison of screen-detected and other tumours showed that the latter were more frequently mammogram-negative and CaN+. Overall five-year survival was 89% and five-year event-free survival 86%. Five-year event-free survival was 100% for CIS, 88% for invasive cancer without nodal or distant spread and 67% for CaN+. CONCLUSIONS: The majority of cancers arising in women at increased genetic risk of breast cancer can be detected by planned screening, even in those under age 50. Surveillance should include regular expert clinical examination and teaching of "breast awareness" as well as mammography. Attention to the logistics of screening programmes may improve still further the proportion of tumours that are screen-detected. The trend towards earlier pathological stage in tumours detected during follow-up rounds and the preliminary findings on survival analysis suggest that this approach will prove to be of long-term benefit for breast cancer families. (+info)
The efficacy of laboratory diagnosis of Helicobacter pylori infections in gastric biopsy specimens is related to bacterial density and vacA, cagA, and iceA genotypes.
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A total of 500 consecutive patients undergoing upper endoscopy were biopsied and tested for H. pylori infection by the Campylobacter-like organism (CLO) test, culture, histology, and PCR. Serum samples were tested by two different serological assays. Patients were considered H. pylori positive if at least two of the four biopsy specimen-based methods yielded positive results. PCR had the highest diagnostic sensitivity (99.4%), followed by histology (92.2%), culture (89.5%), and the CLO test (89.0%). The specificities of all methods were higher than 98%. Of the organisms from the 181 PCR-positive patients, the vacA (s and m regions), cagA, and iceA genotypes were determined by reverse hybridization (line probe assay) or an allele-specific PCR. Organisms that were detected by PCR but that remained undetected by the CLO test were significantly more often vacA s1 (P = 0.006), m1 (P = 0.028), and cagA positive (P = 0.029) than vacA s2, m2, and cagA negative, respectively. Organisms that were detected by PCR but that remained undetected by culture or histology more often contained iceA1 (P = 0. 034 and P = 0.029, respectively) than iceA2. Higher H. pylori density was associated with vacA s2 (P = 0.024), vacA m2 (P = 0.050), and cagA-negative (P = 0.035) genotypes. Also, the diagnostic results of the CLO test (P = 0.001) and culture (P = 0.031) but not those of the PCR (P = 0.130) were significantly associated with the H. pylori density. The rate of detection by the four biopsy specimen-based tests was lower for patients who used proton pump inhibitors, but this was independent of the H. pylori genotypes. These observations may be explained by different bacterial densities, as established by the distinct genotypes of H. pylori, and confirm that the biologies of strains with such genotypes are considerably different. (+info)
Diagnosis of human immunodeficiency virus infection using an immunoglobulin E-based assay.
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Immunoglobulin assays that are sensitive and specific for detecting human immunodeficiency virus type 1 (HIV-1) infection are especially important in developing countries where PCR and viral culture may not be readily available. Immunoglobulin E (IgE), which is elevated in HIV-1 infection, is the only antibody that does not cross the placenta, making it potentially valuable for viral detection in both children and adults. This study developed an assay for detection of HIV specific IgE antibodies in adults. A total of 170 serum samples from 170 adults (116 HIV positive and 54 HIV negative) were analyzed. Serum or plasma samples were treated by using the protein G affinity method. The HIV status was determined by using two IgG enzyme-linked immunosorbent assays (ELISAs) and one Western blot evaluation. The IgE enzyme immunoassay test for HIV-1 correctly identified the HIV status in 98.8% of the samples (168 of 170). One false-positive and one false-negative test occurred with the IgE ELISA, as well as with the IgG ELISA test but were correctly identified by the IgE test. Analysis of the data demonstrated a high specificity (99%) and sensitivity (99%) of the IgE test, with 95% confidence intervals. The IgE assay appears to be sensitive and specific, suggesting that IgE-specific antibodies offer an effective method to detect HIV-1 infection in adults. (+info)
Perioperative frozen section examination in parotid gland tumors.
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CONTEXT: The minimal recommended surgical approach to parotid tumors is partial parotidectomy with resection of the superficial lobe of the gland. Histologic diagnosis prior to surgery is not possible, as incisional biopsies are contraindicated due to the possibility of facial nerve injury or incomplete tumor resection. Thus, the biopsies tend to be perioperative. OBJECTIVE: To compare the results of frozen section examination with the definitive pathological diagnosis. DESIGN: Accuracy study by retrospective analysis. SETTING: Head and Neck Surgery Service of Heliopolis Hospital, Sao Paulo, Brazil. SAMPLE: 153 cases of parotid gland tumors treated between 1977 and 1994. DIAGNOSTIC TEST: Frozen section and pathological diagnosis. MAIN MEASUREMENTS: Sensibility and specificity of the frozen section examination. RESULTS: Frozen section study diagnosed 19 (12.4%) malignant and 127 (83.7%) benign tumors. Sensitivity of the frozen sections for malignancy was 61.5% (95% CI 54 to 69%) and specificity was 98% (95% CI 94 to 100%), and this result is comparable to the literature. CONCLUSIONS: We consider that frozen section examination for salivary gland tumors is not sufficient on its own for deciding on the best management. Their interpretation must be correlated with clinical and intraoperative findings, in association with the surgeon's experience. (+info)
Effects of drugs on glucose measurements with handheld glucose meters and a portable glucose analyzer.
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Thirty drugs used primarily in critical care and hospital settings were tested in vitro to observe interference on glucose measurements with 6 hand-held glucose meters and a portable glucose analyzer. Paired differences of glucose measurements between drug-spiked samples and unspiked control samples were calculated to determine bias. A criterion of +/- 6 mg/dL was used as the cutoff for interference. Ascorbic acid interfered with the measurements on all glucose devices evaluated. Acetaminophen, dopamine, and mannitol interfered with glucose measurements on some devices. Dose-response relationships help assessment of drug interference in clinical use. High dosages of these drugs may be given to critically ill patients or self-administered by patients without medical supervision. Package inserts for the glucose devices may not provide adequate warning information. Hence, we recommend that clinicians choose glucose devices carefully and interpret results cautiously when glucose measurements are performed during or after drug interventions. (+info)
An aggressive intrasinusoidal lymphoma presenting with marked systemic disturbance but normal imaging studies.
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A patient with an aggressive intrasinusoidal non-Hodgkins lymphoma, presenting with marked systemic disturbance but only a mildly raised alkaline phosphatase as a localising sign is described. All imaging studies of the liver were normal and the diagnosis was delayed until a percutaneous liver biopsy was performed. Once diagnosed, the patient responded extremely well to conventional anti-lymphoma chemotherapy. (+info)