Laboratory guidelines for the practical use of HIV drug resistance tests in patient follow-up.

HIV drug resistance is one of the major limitations in the successful treatment of HIV-infected patients using currently available antiretroviral combination therapies. When appropriate, drug susceptibility profiles should be taken into consideration in the choice of a specific combination therapy. Guidelines recommending resistance testing in certain circumstances have been issued. Many clinicians have access to resistance testing and will increasingly use these results in their treatment decisions. In this document, we comment on the different methods available, and the relevant issues relating to the clinical application of these tests. Specifically, the following recommendations can be made: (i) genotypic and phenotypic HIV-1 drug resistance analyses can yield complementary information for the clinician. However, insufficient information currently exists as to which approach is preferable in any particular clinical setting; (ii) when HIV-1 drug resistance testing is required, it is recommended that testing be performed on plasma samples obtained before starting, stopping or changing therapy, on samples that have a viral load above the detection limit of the resistance test; (iii) the panel recommends that genotypic and phenotypic HIV-1 drug resistance testing for clinical purposes be performed in a certified laboratory under strict quality control and quality assurance standards; and (iv) the panel recommends that resistance testing laboratories provide clinicians with resistance reports that include a list of drug-related resistance mutations (genotype) and/or a list of drug-related fold resistance values (phenotype), with interpretations of each by an experienced virologist. The interpretation of genotypic and phenotypic analysis is a complex and developing science, and in order to understand HIV-1 drug resistance reports, communication between the requesting clinician and the expert that interpreted the resistance report is recommended.

European multicentre evaluation of the ABBOTT Spectrum clinical chemistry analyzer.

The analytical performance of the selective multitest ABBOTT Spectrum analyser was studied according to the ECCLS guidelines and partly the CERMAB protocol in a multicentre evaluation involving laboratories from six European countries. Fifteen analytes, including the electrolytes sodium, potassium and chloride, were measured each in at least 3 laboratories, all at 37 degrees C, except the electrolytes, which are measured at room temperature. The trial lasted approximately three months and involved the collection of over 60,000 data points. It yielded the following results: 1. The precision was at least as good as the precision obtained with the comparison instruments. The majority of the coefficients of variation were between 1 and 4%. 2. The recovery for method assigned control sera values was, with few exceptions, within 10%. 3. Good agreement with respect to the method assigned values of control materials and method comparison with patient specimens to different instruments (e.g. SMAC, Hitachi 737, RA 1000) was found. 4. No drift was observed. 5. Reagent-related carry-over was not found. Specimen-related carry-over was detected in some cases, the deviation being of little or no clinical significance. 6. The manufacturer's claims regarding method linearity were as stated or exceeded. 7. The open system capability was tested and rated as very convenient. 8. The practicability of the instrument was very good.

Post-cardiac injury syndrome and an increased humoral immune response against the major contractile proteins (actin and myosin).

To better understand the pathogenesis of the post-cardiac injury syndrome (PCIS) 2 models of cardiac injury were studied. One hundred twenty-nine patients who underwent cardiac surgery and 80 patients with acute myocardial infarction (AMI) were prospectively followed and the levels of anti-heart antibodies (AHA), anti-actin antibodies (AAA) and anti-myosin antibodies (AMA) were determined. In the surgical group, PCIS developed in 27 patients (21%) and incomplete PCIS in 36 (28%). In the AMI group, PCIS did not develop in any patient, but incomplete PCIS developed in 11 patients (14%) (p less than 0.001). The surgical group showed a significantly higher humoral immune response than the AMI group when analyzed for AHA and anti-contractile protein antibodies. After cardiac surgery, AHA developed in 59 patients (46%), AAA developed in 33 (26%) and AMA developed in 49 (38%); in the AMI group, significant levels of AHA, AAA and AMA developed in 16 (20%), 7 (9%) and 13 patients (16%), respectively. These studies show a significant correlation between the PCIS clinical classification and auto-antibodies raised against heart contractile proteins.

Detection of anti-contractile antibodies after cardiac surgery using ELISA assay.

Sera from 196 patients were collected before and after cardiac surgery to measure antibodies against heart tissue and against actin and myosin. In the post-operative period antibodies were found in 87 patients (44%) producing a cross-striated fluorescence pattern in heart tissue. Antibodies against the major contractile proteins were found in 91 patients (46%), anti-actin antibodies in 49 patients (25%) and anti-myosin antibodies in 65 patients (33%). We found a significant correlation (P less than 0.0001) between the antibodies producing a cross-striated fluorescence pattern and antibodies recognizing contractile proteins. These results suggest that contractile proteins evoke an immune response after cardiac surgery and that this response may compromise cardiac function.