Validation of immune-complex enzyme immunoassays for diagnosis of pneumococcal pneumonia among adults in Kenya.
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The efficacy of pneumococcal vaccines in protecting against pneumococcal pneumonia can feasibly be measured only with a diagnostic technique that has a high specificity (0.98 to 1.00) and a sensitivity greatly exceeding that of blood cultures (>0.2 to 0.3). In this context immune-complex enzyme immunoassays (EIAs) offer a novel, convenient diagnostic method, and we have investigated three such assays with appropriate study populations in Kenya. Sera from 129 Kenyan adults with pneumococcal pneumonia and 97 ill controls from the same clinics, but without pneumococcal disease syndromes, were assayed with immune-complex EIAs for pneumolysin, C-polysaccharide, and mixed capsular polysaccharides (Pneumovax II). At an optical density (OD) threshold yielding a specificity of 0.95, the sensitivities (95% confidence intervals) of the assays were 0.22 (0.15 to 0.30), 0.26 (0.19 to 0.34), and 0.22 (0.15 to 0.29), respectively. For pneumolysin immune complexes, human immunodeficiency virus (HIV)-positive patients had a higher mean OD than HIV-negative patients (639 versus 321; P < 0.0001), but stratification by HIV infection status did not alter the performance of this test. Combining the results of all three EIAs did not enhance the diagnostic performances of the individual assays. In Kenyan adults the sensitivities of the immune-complex EIAs could exceed that of blood cultures only at levels of specificity that were insufficient for the performance of vaccine efficacy studies. (+info)
Recombinational and mutational hotspots within the human lipoprotein lipase gene.
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Here an analysis is presented of the roles of recombination and mutation in shaping previously determined haplotype variation in 9.7 kb of genomic DNA sequence from the human lipoprotein lipase gene (LPL), scored in 71 individuals from three populations: 24 African Americans, 24 Finns, and 23 non-Hispanic whites. Recombination and gene-conversion events inferred from data on 88 haplotypes that were defined by 69 variable sites were tested. The analysis revealed 29 statistically significant recombination events and one gene-conversion event. The recombination events were concentrated in a 1.9-kb region, near the middle of the segment, that contains a microsatellite and a pair of tandem and complementary mononucleotide runs; both the microsatellite and the runs show length variation. An analysis of site variation revealed that 9.6% of the nucleotides at CpG sites were variable, as were 3% of the nucleotides found in mononucleotide runs of >/=5 nucleotides, 3% of the nucleotides found +info)
The false-positive parathyroid sestamibi: a real or perceived problem and a case for radioguided parathyroidectomy.
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OBJECTIVE: To demonstrate that the positive parathyroid sestamibi scan, if correctly interpreted and applied, truly represents a parathyroid adenoma, never a "false-positive" scan. SUMMARY BACKGROUND DATA: Although the sestamibi scan is widely ordered preoperatively to locate parathyroid adenomas, concern about a false-positive scan often causes surgeons to distrust the results. Tissues such as thyroid adenomas and lymph nodes have been blamed for false-positive studies, but the radioactivity of these presumed false-positive tissues has never been measured. METHODS: Over an 1 8-month period, 17 patients were referred for persistent primary hyperparathyroidism after undergoing at least one neck exploration. All patients had a sestamibi scan prior to their initial operation that was interpreted as clearly positive and then, during or after an unsuccessful operation, deemed false-positive by the surgeon. At the authors' institution, all patients underwent repeat sestamibi scintigraphy and were taken to the operating room while radioactive for a minimally invasive radioguided parathyroidectomy (MIRP). RESULTS: The authors' sestamibi scans demonstrated the same single focus of radioactivity displayed on the outside scans, clearly positive. During MIRP, an adenoma was successfully located and removed in all patients, with confirmation of the diagnosis by quantitative differential radioactivity and subsequent histologic examination. Removal of the radioactive tissue cured all patients. CONCLUSION: Intraoperative nuclear mapping permitted identification and removal of parathyroid adenomas in all patients with positive sestamibi scans that had previously been labelled false-positive, indicating that each patient would have been cured during their previous operation if radioguided techniques were used. Surgeons should be extremely cautious in deciding intraoperatively that a positive sestamibi scan is a false-positive scan. (+info)
False positive head-up tilt: hemodynamic and neurohumoral profile.
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OBJECTIVES: This study examined differences in mechanisms of head-up tilt (HUT)-induced syncope between normal controls and patients with neurocardiogenic syncope. BACKGROUND: A variable proportion of normal individuals experience syncope during HUT. Differences in the mechanisms of HUT-mediated syncope between this group and patients with neurocardiogenic syncope have not been elucidated. METHODS: A 30-min 80 degrees HUT was performed in eight HUT-negative volunteers (Group I), eight HUT-positive volunteers (Group II) and 15 patients with neurocardiogenic syncope. Heart rate and blood pressure (BP) were monitored continuously. Epinephrine and norepinephrine plasma levels, as well as left ventricular dimensions and contractility determined by echocardiography, were measured at baseline and at regular intervals during the test. RESULTS: The main findings of this study were the following: 1) All parameters were similar at baseline in the three groups; and 2) During tilt: a) the time to syncope was shorter in Group III than in group II (9.5 +/- 3 vs. 17 +/- 3 min p < 0.05); b) there was an immediate, persisting drop in mean BP in Group III; c) the decrease rate of left ventricular end-diastolic dimensions was greater in Group III than in Group II or Group I (-1.76 +/- 0.42 vs. -0.87 +/- 0.35 and -0.67 +/- 0.29 mm/min, respectively, p < 0.05); d) the leftventricular shortening fraction was greater in Group III than in the other two groups (39 +/- 1 vs. 34 +/- 1 and 32 +/- 1%, respectively, p < 0.05); and e) although the norepinephrine level remained comparable among the groups, there was a significantly higher peak epinephrine level in Group III than in Group II and Group I (112.3 +/- 34 vs. 77.6 +/- 10 and 65 +/- 12 pg/ml, p < 0.05). CONCLUSIONS: Mechanisms of syncope during HUT appeared to be different in normal volunteers and patients with neurocardiogenic syncope. In the latter, there was evidence of an impaired vascular resistance response from the beginning of the orthostatic challenge. Furthermore, in the patients there was more rapid peripheral blood pooling, as indicated by the echocardiographic measurements of left ventricular end-diastolic changes, leading to more precocious symptoms. In syncopal patients, the higher level of plasma epinephrine probably mediated the increased cardiac contractility and possibly contributed to the impaired vasoconstrictive response. (+info)
Factors associated with positive predictability of the anti-HCV ELISA method with confirmatory RT-PCR.
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The positive predictability of anti-HCV ELISA is low, especially, in blood donors and in healthy populations. False positive anti-HCV results pose some difficulties in medical practice and in blood screening. The aim of this study was to identify the factors associated with true hepatitis C virus (HCV) infection among anti-HCV ELISA-positives. A case-control analysis was conducted using 354 subjects who were positive for anti-HCV ELISA. All subjects were tested for true HCV infection using the reverse transcriptase polymerase chain reaction (RT-PCR). Tests for serum alanine aminotransferase (ALT), fasting glucose, HBsAg, anti-HBc antibody, alpha-fetoprotein, platelet count and ultrasound of liver were also performed. Epidemiological data were obtained by self-administered questionnaires. Out of 354 subjects, 202 (57.1%) were positive for HCV by RT-PCR and 152 were negative and used as the control group. In multivariate analysis, blood transfusion (odds ratio, OR 2.3, 95% confidence interval, CI 1.3-4.0), elevated ALT (OR 2.2, 95% CI 1.2-4.3) and higher anti-HCV ELISA ratios (more than 3; OR 1.7, 95% CI 1.3-2.1) were associated with true HCV infection. Thrombocytopenia was also associated with the presence of HCV in univariate analysis. These results suggest that a history of blood transfusion, elevated ALT and a high score on anti-HCV ELISA ratios are associated with true HCV infection among anti-HCV ELISA-positives. (+info)
The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide.
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OBJECTIVE: Since modern treatment of rheumatoid arthritis (RA) is shifting toward aggressive antirheumatic therapy in an early phase of the disease, diagnostic tests with high specificity are desirable. A new serologic test (anti-cyclic citrullinated peptide [anti-CCP] enzyme-linked immunosorbent assay [ELISA]) was developed to determine the presence of antibodies directed toward citrullinated peptides, using a synthetic peptide designed for this purpose. METHODS: A cyclic peptide variant that contains deiminated arginine (citrulline) was designed and used as antigenic substrate in ELISA. Test parameters and diagnostic characteristics of the test were studied in patients with and without RA, in patients with various infectious diseases, and in a group of patients from an early arthritis clinic (EAC). RESULTS: Using prevalent RA and non-RA sera, the anti-CCP ELISA proved to be extremely specific (98%), with a reasonable sensitivity (68%). Also, in the EAC study group, the anti-CCP ELISA appeared to be highly specific for RA (96%). In comparison with the IgM rheumatoid factor (IgM-RF) ELISA, the anti-CCP ELISA had a significantly higher specificity (96% for CCP versus 91% for IgM-RF; P = 0.016) at optimal cut-off values. The sensitivity of both tests for RA was moderate: 48% and 54% for the anti-CCP ELISA and the IgM-RF ELISA, respectively (P = 0.36). Combination of the anti-CCP and the IgM-RF ELISAs resulted in a significantly higher positive predictive value of 91% (P = 0.013) and a slightly lower negative predictive value of 78% (P = 0.35) as compared with the use of the IgM-RF ELISA alone. The ability of the 2 tests performed at the first visit to predict erosive disease at 2 years of followup in RA patients was comparable (positive predictive value 91%). CONCLUSION: The anti-CCP ELISA might be very useful for diagnostic and therapeutic strategies in RA of recent onset. (+info)
BACKGROUND: Ultrasound, genetic and clinical correlations are available for ADPKD-1, but lacking for ADPKD-2. The present study was carried out to address: (i) the age-related diagnostic usefulness of ultrasound compared with genetic linkage studies; (ii) the age-related incidence and prevalence of relevant symptoms and complications; and (iii) the age and causes of death in patients with ADPKD-2. METHODS: Two hundred and eleven alive subjects, from three ADPKD-2 families at 50% risk, were evaluated by physical examination, consultation of hospital records, biochemical parameters, ultrasound and with genetic linkage and DNA mutation analyses. Nineteen deceased and affected family members were also included in the study. RESULTS: Of the 211 alive members, DNA linkage studies and direct mutation analyses showed that 106 were affected and 105 were not. Ultrasound indicated 94 affected, 108 not affected and nine equivocal results in nine children under the age of 15. For all ages, the false-positive diagnostic rate for ultrasound was 7.5% and the false-negative rate was 12.9%. The difference between ultrasound and DNA findings was most evident in children aged 5-14 years where the ultrasound was correct in only 50% and wrong or inconclusive in the remaining 50%. The mean age of the 106 alive, ADPKD-2 genetically affected patients was 37.9 years (range: 6-66 years). Among them, 23.5% had experienced episodes of renal pain, 22.6% were treated for hypertension, 22.6% had experienced at least one urinary tract infection, 19.8% had nephrolithiasis, 11.3% had at least one episode of haematuria, 9.4% had asymptomatic liver cysts, 7.5% had developed chronic renal failure and 0.9% had reached end-stage renal failure. Of the 19 deceased members, nine died before reaching end-stage renal failure at a mean age of 58.7 years (range: 40-68 years), mainly due to vascular complications, while the remaining 10 died on haemodialysis at a mean age of 71.4 years (range: 66-82 years). CONCLUSIONS: DNA analysis is the gold standard for the diagnosis of ADPKD-2, especially in young people. Ultrasound diagnosis is highly dependent on age. Under the age of 14, ultrasound is not recommended as a routine diagnostic procedure, but ultrasound becomes 100% reliable in excluding ADPKD-2 in family members at 50% risk, over the age of 30. ADPKD-2 represents a mild variant of polycystic kidney disease with a low prevalence of symptoms and a late onset of end-stage renal failure. (+info)
Surveillance for recurrent head and neck cancer using positron emission tomography.
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PURPOSE: Earlier detection of head and neck cancer recurrence may improve survival. We evaluated the ability of [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) to detect recurrence in a prospective trial using sequential PET scans. PATIENTS AND METHODS: Serial posttherapy FDG-PET was prospectively performed in 44 patients with stage III or IV head and neck cancer. PET was performed twice during the first posttreatment year (at 2 and 10 months after therapy) and thereafter as needed. After therapy, patients were grouped, based on tissue biopsies, into those who achieved a complete response (CR) and those who had residual disease (RD). Patients who achieved a CR were further grouped into those without evidence of disease and those who had recurrence by 1 year after completion of therapy. Disease status as determined by physical examination (PE), PET, and correlative imaging was compared. RESULTS: Eight patients were lost to follow-up and six had RD after therapy. Of the remaining 30 patients with a CR, 16 had recurrence in the first year after therapy. Five of these 16 patients had recurrence detected by PET only, four by PET and correlative imaging only, five by PE and PET only, and two by PE, correlative imaging, and PET. Only PET detected all recurrences in the first year. PET performed better than correlative imaging (P =.013) or PE (P =.002) in the detection of recurrence. CONCLUSION: PET can detect head and neck tumor recurrence when it may be undetectable by other clinical methods. FDG-PET permits highly accurate detection of head and neck cancer recurrence in the posttherapy period. (+info)