Cyclooxygenase-2 inhibitor-associated minimal-change disease.

Selective cyclooxygenase-2 (COX-2) inhibitors are relatively newer anti-inflammatory drugs that produce comparable antiinflammatory and analgesic effects to the nonselective nonsteroidal antiinflammatory drugs (NSAIDs); but with fewer symptomatic gastric and duodenal ulcers. Limited data are available concerning the toxicity associated with COX-2 inhibitors outside the gastrointestinal tract. The NSAIDs have been known for their nephrotoxic potentials including minimal-change disease (MCD) with interstitial nephritis. Although the recent data suggests that COX-2 inhibitors may have the same adverse renal effect as NSAIDs, there is only one case report describing minimal change disease and acute interstitial nephritis (AIN) associated with a COX-2 inhibitor, celecoxib. We are reporting a case of MCD and acute tubular necrosis (ATN) but without interstitial nephritis in a patient treated with celecoxib. Although the proteinuria in our patient resolved completely after discontinuation of celecoxib, the renal function did not. We suggest that heightened suspicion of this side effect of COX-2 inhibitors should be maintained in all patients taking this class of drugs who present with nephrotic syndrome.

Plasmapheresis as an effective treatment for opsoclonus-myoclonus syndrome.

A 6-year-old female diagnosed with idiopathic opsoclonus-myoclonus syndrome at 22 months of age who failed to respond to treatment with adrenocorticotropic hormone (ACTH), IV gammaglobulin (IVIG), and azathioprine is presented. Because of marked and progressive deterioration in motor function and speech, this patient received a course of plasmapheresis with concomitant steroids and azathioprine. Within 1 week, marked improvements in motor function were noted. Eighteen months later, the patient ambulates, walks without support, and attends a regular school in the appropriate grade level.

Cyclosporine and chronic sarcoidosis.

Two patients with progressive sarcoidosis who had poor responses and side effects from corticosteroid therapy were treated with cyclosporine. Cyclosporine suppressed conventional markers of inflammation and there was clinical improvement in one patient, but the disease recurred when therapy was discontinued. The second patient who had diabetes mellitus developed unstable glucose metabolism when given cyclosporine. This unstable diabetes mellitus together with side effects of nausea and vomiting resulted in weight loss and inadequate serum therapeutic levels that was associated with a poor therapeutic response to the cyclosporine. The major side effects in both patients were headache and gastrointestinal symptoms, but there was no renal dysfunction. We conclude that while corticosteroids remain the mainstay of sarcoid therapy, when these drugs have not been successful for the skin manifestations of the disease, a trial of cyclosporine may be justified.

High levels of Epstein-Barr virus in the oropharynx: a predictor of disease progression in human immunodeficiency virus infection.

The role of Epstein-Barr virus (EBV) on the progression of human immunodeficiency virus (HIV) infection is not well defined. The objective of this prospective study was to determine the prevalence of EBV excretion and the role that EBV might have on HIV disease progression. Fifty-two homosexual males were studied, all of whom had positive EBV serology. Twenty-four of the 27 HIV-seropositive and 14 of the 25 HIV-seronegative subjects had detectable levels of EBV DNA in oropharyngeal cells. In addition to a greater prevalence of detectable EBV, the level of excretion was higher among HIV-seropositives than among HIV-seronegatives, and higher among group III than among group II HIV-seropositive men. These results are consistent with earlier studies showing a relationship between immunosuppression and EBV reactivation. The EBV excretion levels in a control group of 52 age-matched heterosexual males were substantially lower than those found in the homosexual group. In a proportional hazards regression analysis EBV excretion was found to be the best single predictor of progression of HIV infection (P less than 0.001). HIV p24 core antigenemia (P = 0.048) and low EBNA (P = 0.024) were significant predictors independent of EBV excretion. Whether EV directly accelerates the time to progression or is merely a marker of underlying subclinical immunosuppression remains an open question.

An alternative approach for statistical analysis of kidney transplant data: multivariate analysis of single-center experience.

To avoid the center effect and the possible hidden interactions of multicenter studies, the validity of the Cox Proportional Hazards Model for the analysis of a single-center kidney transplant program was tested, considering 287 renal transplants performed in a 10-year period. The inclusion of type of donor and main immunosuppressive drug as covariates in the model did not violate the proportionality assumption of the Cox model. According to this method, the following covariates were significant in predicting graft survival: cyclosporine, type of donor, good human leukocyte antigen (HLA)-A and HLA-B match (DR data were not considered), highest percentage of reactive antibodies against panel cells, and nephroangiosclerosis as a primary renal disease. Cyclosporine did not significantly improve graft survival in living related donor transplants. Pretransplant blood transfusions, cold ischemia time, and donor ABO blood group were initially significant but dropped out in the step-down procedure. Recipient's age at transplant, cyclosporine, HLA-A and HLA-B match, and nephroangiosclerosis were significant in predicting patient survival. It was concluded that using long-term data of cadaveric and living related renal transplants either on azathioprine or cyclosporine is a valid way to perform multivariate analysis of single-center transplant programs that do not have large samples.

Human T cell subset ratio quantitation by 51Cr release: assessment of a new technique.

A method for T cell subset ratio quantitation is described. This technique makes use of monoclonal antibodies 66.1 (OKT4 equivalent) and 51.1 (OKT8 equivalent) in complement-dependent cytotoxicity. The percentages of 51Cr release with these 2 reagents from peripheral blood lymphocyte targets were used to calculate the ratio. It is simple, inexpensive, and can be used for large numbers of samples, but is less accurate when compared with the microscopic technique in immunofluorescence. It may serve as a screening test in certain clinical situations where there is need to determine the T4/T8 ratio.

Measures of immunologic and inflammatory responses in vitro in rheumatoid patients treated with methotrexate.

We examined the effects of low dose parenteral methotrexate (MTX) on immunologic and inflammatory responses of potential importance in the pathogenesis of rheumatoid arthritis. Only 2 significant changes were noted: the number of esterase positive cells in the peripheral blood decreased, and the uptake of tritiated thymidine by incubated peripheral blood mononuclear cells fell markedly. These changes were present 48 h after an injection of MTX, before decreased disease activity became clinically apparent. We therefore conclude that they were direct effects of the drug itself.

Cyclosporine-associated lymphoproliferation, despite controlled cyclosporine blood concentrations, in a renal allograft recipient.

In a patient receiving sulfinpyrazone (Anturan, Geigy) an unusually high dose of cyclosporine (Cys) was required to maintain serum values in the range of 50-200 ng/ml. After eight months of 1300-1500 mg/day, the patient complained of increasing malaise and symptoms of cyclosporine side-effects. This clinical state was accompanied by splenomegaly and two monoclonal peaks in the gamma region on serum electrophoresis. Concomitantly, rising cytomegalovirus IgM titres, following by rising IgG titres, indicated a primary cytomegalovirus infection. This ominous biclonal proliferation markedly diminished during the subsequent six months, during which time the cyclosporine dose was minimised. He returned to good health, splenomegaly and monoclonal gamma globulin virtually disappearing. He remains well at 16 months post-transplantation.

Induction of suppressor cells in autologous mixed lymphocyte culture (AMLC) in humans.

T cells stimulated for 6-7 days in autologous mixed lymphocyte culture (AMLC) showed suppressive effects when added to fresh mixed cultures where autologous lymphocytes (A) were stimulated by Mitomycin C-treated allogeneic lymphocytes (Xm), in a ratio of A:Xm:AMLC-activated cells of 1:1:0.5. Both cytotoxic and proliferative activities in second cultures, as assayed after 6 days of incubation, were significantly inhibited (percentage suppression of cytotoxic activity observed in 17 experiments was 75.3 +/- 22.4; percentage suppression of proliferation was 60.6 +/- 18.2). Suppressor cells (SC) generated in AMLC were Mitomycin C sensitive and nonspecific in their action; not only A/Xm but also X/Am and X/Ym cultures were suppressed to the same extent. AMLC-Activated cells showed a considerable degree of proliferation in response to alloantigens but failed to express any cytotoxic activity against autologous or allogeneic phytohemagglutinin blasts. Thus, the inhibitory effect observed in this system is not due to cytotoxic elimination of responding or stimulating cells in the second culture but rather reflects a true regulatory (suppressive) mechanism.

Antibody-mediated cellular cytotoxicity against Raji cells ADCC(Raji): evaluation of false positives in the detection of circulating immune complexes by Raji-cell assay.

Raji-cell radioimmunoassay is a very sensitive and reproducible method for the detection of circulating immune complexes. Using a complement-independent, antibody-dependent cellular cytotoxicity assay against 51Cr-labeled Raji cells, there is no correlation between activity against Raji cells and positivity in Raji-cell radioimmunoassay for circulating immune complexes in three sets of sera (from renal transplantation patients, multiparous women, and patients suffering from systemic lupus erythematosus). We conclude that IgG antibodies to Raji membranes are not a significant cause of false-positive results in circulating immune complexes as detected by Raji-cell radioimmunoassay.