The PROgnostic Value of unrequested Information in Diagnostic Imaging (PROVIDI) Study: rationale and design.

We describe the rationale for a new study examining the prognostic value of unrequested findings in diagnostic imaging. The deployment of more advanced imaging modalities in routine care means that such findings are being detected with increasing frequency. However, as the prognostic significance of many types of unrequested findings is unknown, the optimal response to such findings remains uncertain and in many cases an overly defensive approach is adopted, to the detriment of patient-care. Additionally, novel and promising image findings that are newly available on many routine scans cannot be used to improve patient care until their prognostic value is properly determined. The PROVIDI study seeks to address these issues using an innovative multi-center case-cohort study design. PROVIDI is to consist of a series of studies investigating specific, selected disease entities and clusters. Computed Tomography images from the participating hospitals are reviewed for unrequested findings. Subsequently, this data is pooled with outcome data from a central population registry. Study populations consist of patients with endpoints relevant to the (group of) disease(s) under study along with a random control sample from the cohort. This innovative design allows PROVIDI to evaluate selected unrequested image findings for their true prognostic value in a series of manageable studies. By incorporating unrequested image findings and outcomes data relevant to patients, truly meaningful conclusions about the prognostic value of unrequested and emerging image findings can be reached and used to improve patient-care.

Studies of an improved rhesus hematopoietic progenitor cell assay.

We have improved Rhesus monkey marrow cell growth in semisolid media by means of substituting supplemented calf serum for fetal bovine serum. The cloning efficiency of light-density marrow cells separated on 60% Percoll was 126 (+/- 54)/10(5) (n = 12, +/- SD), and for light-density peripheral blood cells 60 (+/- 46)/10(6) (n = 11). Thirty-five percent of the colonies were multilineage, whereas the remainder were unilineage colonies composed of erythrocytes, megakaryocytes, and neutrophilic or monocytic granulocytes. Unilineage megakaryocyte colonies comprised 12% of the total marrow progenitor cells. The [3H]TdR suicide index of marrow progenitor cells was 47% +/- 9% (n = 12). This progenitor cell assay should prove useful in preclinical studies of the effect of recombinant hematopoietic growth factors on the number and cycling status of Rhesus hematopoietic progenitor cells.

Effect of cyclosporin on serum creatinine in patients with rheumatoid arthritis.

Serum creatinine levels were measured before, during and after the administration of cyclosporin (Cy) in a double-blind placebo-controlled study in patients with rheumatoid arthritis (RA). The level rose significantly during and after Cy therapy, whereas the initial serum creatinine value did not change in the placebo group. The increase in the Cy group was not correlated with the mean Cy blood level. The rise in serum creatinine during Cy therapy was gradual and was not significantly correlated with the initial creatinine level; relative to the pretreatment value, the post-treatment increase was significantly correlated with the increase during Cy therapy. It is concluded that Cy administration for not more than 6 months, and at a maximum dosage of 10 mg/kg for 2 months, leads to an irreversible loss of more than 10% of renal function in RA patients. The damage may be ascribed to the combination of Cy with other factors compromising the kidneys, e.g., the use of non-steroidal anti-inflammatory drugs in the potentially systemic disorder of RA.

Cyclosporin treatment for rheumatoid arthritis: a placebo controlled, double blind, multicentre study.

The efficacy and safety of cyclosporin for patients with rheumatoid arthritis (RA) were assessed in a six month double blind, placebo controlled, multicentre study. The initial dosage of the drug was 10 mg/kg daily for two months. There were many discontinuations in both the cyclosporin group (eight out of 17) and the placebo group (six out of 19). Of the patients who completed the six months of therapy, those who had received cyclosporin showed a significant improvement in the number of swollen joints, the Ritchie articular index, and pain at active movement and at rest, compared not only with their condition at the start of the study, but also with the end results of the placebo group. Major adverse reactions to the drug were gastrointestinal disturbances and nephrotoxicity, which were probably due to the relatively high dosages of cyclosporin given in combination with non-steroidal anti-inflammatory drugs.