Scleroderma treatment differs between experts and general rheumatologists.
Explore the source record for details and available documents.
Comorbidity↗
Biomedical subjects
Adriana Krizova
Publications and source records attributed to Adriana Krizova.
Hypersensitivity of HIV-1-infected cells to reactive sulfonamide metabolites correlated to expression of the HIV-1 viral protein tat.
Impairment of human immunodeficiency virus (HIV)-infected cells to deal with reactive drug metabolites may be a mechanism for the increased rate of adverse drug reactions seen in AIDS. HIV Tat protein expression may be associated with increased oxidative stress within HIV-infected cells. To determine the relationship between expression of HIV Tat and sensitivity to reactive drug metabolites, we studied toxicity of sulfamethoxazole (SMX) and its reactive hydroxylamine intermediate (SMX-HA) in lymphocytes transfected with the HIV tat gene. Over a concentration range from 0 to 400 microM SMX-HA, there was a significant concentration-dependent increase in cell death in transfected cell lines expressing Tat compared with controls. Jurkat T cells transfected with a dose-dependent inducible tat gene showed increased toxicity in response to SMX-HA as more Tat expression was induced. Enhanced sensitivity to SMX-HA was accompanied by significantly lower concentrations of total intracellular glutathione compared with controls (P < 0.05). Sensitivity to reactive drug metabolites in HIV-infected cells seems to be mediated by the viral protein Tat.
Cell Line↗
Close association of herpes zoster reactivation and systemic lupus erythematosus (SLE) diagnosis: case-control study of patients with SLE or noninflammatory musculoskeletal disorders.
OBJECTIVE: To investigate the prevalence of infections, particularly the frequency of shingles and the timing of varicella zoster virus (VZV) reactivation, and antibiotic use, vaccinations, and joint trauma prior to and at diagnosis of systemic lupus erythematosus (SLE). METHODS: We sent questionnaires to patients with SLE (n = 93) and controls with noninflammatory musculoskeletal disorders (MSK; n = 353) including osteoarthritis, fibromyalgia, and tendonitis. We matched SLE patients to controls for sex (up to 1:3). RESULTS: The response rate in SLE was 66% and in controls 69% (p < 0.53). Four of 61 SLE patients and 12 of 173 controls were men. The mean disease duration in the SLE group was 8 +/- 1 years compared to 10 +/- 1 years in controls (p < 0.23). SLE patients were significantly younger than controls (mean age of SLE patients 49 +/- 2 vs 57 +/- 1 years for controls; p < 0.0004), and results were adjusted for age. A significantly higher proportion of SLE participants had a history of VZV (shingles) (19% vs 7%, respectively; OR 2.98, p < 0.003), whereas rubella was reported less in SLE (23% vs 42%; OR 0.43, p < 0.03). VZV infections were clustered just prior to or after diagnosis in SLE but were more widely spaced temporally in the controls (1 +/- 4.5 years after the diagnosis of SLE vs -14.7 +/- 4 years before the diagnosis of noninflammatory MSK disorder; p < 0.003). Diagnosis of shingles was observed in 6 of 11 SLE patients within +/- 2 years of SLE diagnosis, whereas only 2 of 15 controls had shingles within +/- 2 years of diagnosis (OR 7.2, p < 0.03). Only 2 patients with SLE were taking immunosuppressive drugs or steroids at time of shingles, so immunosuppressive therapy was not usually concomitant at time of VZV reactivation. Common infections (respiratory, urinary tract, ear, and eye) in the SLE group exceeded controls, but not significantly (23% vs 9%; OR 2.98, p < 0.06) and SLE patients were more likely to have been vaccinated since 18 years of age with any type of vaccine (69% vs 51%; OR 2.21, p < 0.04). SLE patients were less likely than controls to report joint trauma within one year prior to their diagnosis (25% vs 40%; OR 0.49, p < 0.04). There were no differences with respect to streptococcal throat infection (p < 0.96), diarrhea/vomiting (p < 0.84), rash with fever (p < 0.07), parvovirus infection (p < 0.16), infection after surgery (p < 0.58), respiratory tract infection (p < 0.71), or ear (p < 0.09) and eye infection (p < 0.68) one year prior to diagnosis. A higher proportion of SLE patients had a history of urinary tract infections (46% vs 25%), but this was not significant (p < 0.17), nor was it significant one year prior to diagnosis (p < 0.63). Overall, the likelihood of having any infection one year prior to diagnosis was not significantly higher in the SLE group (p < 0.56). There were no differences one year prior to diagnosis in travel history (p < 0.69), hospitalizations (p < 0.47), use of antibiotics (p < 0.54), history of rheumatic fever, positive TB skin test, or hepatitis A, B or C infection. CONCLUSION: Varicella reactivation as shingles is increased in patients with SLE and clusters around diagnosis. Vaccinations are increased in those with SLE compared to controls. Common infections are not significantly increased in SLE patients prior to onset of symptoms. We cannot determine if VZV infections are causally associated with SLE in some people, are from an abnormal immune system response due to the lupus itself or from the use of steroids or other immunosuppressive drugs to control the disease, or are spurious.
Case-Control Studies↗
Frequency of adverse drug reactions in patients with systemic lupus erythematosus.
OBJECTIVE: The literature suggests that patients with systemic lupus erythematosus (SLE) have a higher frequency of adverse drug reactions (ADR). We performed this case control study to compare the prevalence of ADR in patients with SLE and controls with inflammatory arthritis. METHODS: We surveyed 249 patients, 145 with SLE and 104 age and sex matched controls with other types of inflammatory arthritis, such as rheumatoid arthritis (RA), probable RA, and psoriatic arthritis. We asked about exposure and ADR to the following classes of drugs: (1) beta-lactam antibiotics, (2) sulfonamides, (3) other antibiotics, (4) disease modifying antirheumatic drugs (DMARD), and (5) nonsteroidal antiinflammatory drugs (NSAID). Personal and family atopic histories were obtained. The 2 groups were obtained from a single rheumatologic practice and had similar characteristics and drug exposures. RESULTS: The response rate was 63% in the SLE patients and 64% in the control group. The mean age was 47.8 +/- 1.5 years in patients with SLE and 46.1 +/- 1.7 years in controls (p < 0.51). Ninety-two percent of SLE patients and 88% of controls were female (p < 0.42). Both groups had been exposed similarly to all antibiotics, as there were no significant differences between groups (exposure to sulfa antibiotics 53% in SLE patients vs 46% in controls), and to NSAID (84% SLE group vs 93% controls). Few patients from the SLE group had DMARD exposure, with the exception of plaquenil (65% SLE group vs 30% controls; p < 0.0001) and azathioprine (18% SLE group vs 4% controls; p < 0.006). There were between-groups differences with respect to total number of ADR with sulfa antibiotics (exposed had 25/48 reactions in SLE group vs 6/31 in controls; p < 0.003), but not with other drugs. Most ADR to sulfa antibiotics were cutaneous (rash). Subjects with an allergic or atopic history had more ADR (p < 0.0005). There were no differences between SLE patients and controls in having an allergic history (p < 0.88). Subjects with a positive family history of allergies were more likely to have ADR (p < 0.0043). SLE patients and controls with a personal versus family history of environmental allergies did not differ in having ADR (p < 0.16 and p < 0.83, respectively). CONCLUSION: Both intolerances and true allergic reactions were not dissimilar in patients with SLE compared to controls with inflammatory arthritis, with the exception of cutaneous reactions to sulfa antibiotics in SLE patients. This has not been the experience of other investigators (with increased ADR with several antibiotics in SLE groups) who used healthy, best friend, and relative controls with dissimilar frequencies of drug exposures. Perhaps differences observed in the past (where SLE patients have more ADR than healthy controls) are true of other inflammatory arthritis subjects (who have different drug exposures than healthy individuals) rather than just SLE. Differences could also exist in the pharmacogenetics, as our sample population was mostly Caucasian.
Angioedema↗
Are subjects satisfied with the informed consent process? A survey of research participants.
OBJECTIVE: Letters of information (LOI) for clinical trials are becoming longer and more complicated. We investigated patients' perspectives of their ability to understand the information presented during a clinical trial. Satisfaction with and motivation for participation in clinical trials were also ascertained. Perceptions from various treatment disciplines were compared. METHODS: Participants were chosen from 14 clinical trials (departments of rheumatology, ophthalmology, and cardiology) conducted at the same university. Subjects were asked to complete a written questionnaire that assessed demographic information, recall and understanding of information, subjects' decisions to participate, and perceptions/opinions of the study. The response rate was 75% (rheumatology, n = 74; ophthalmology, n = 32; cardiology, n = 84). RESULTS: The majority of respondents (98%) indicated that they were satisfied with the informed consent process and with their involvement in a trial (97%). Subjects who reported having understood the LOI had better recall of placebo/active drug comparator (p < 0.03), and better understanding of why placebo was used (p < 0.04). No differences were found between those who reported understanding and those who did not on understanding the concept of concealed allocation (blinding). Subjects who felt they had received "the right amount of information" were more likely not to understand concealed allocation. The most frequent reason for trial participation was to help medical science (80%). Subjects with higher education were more likely to understand the reason for placebo use (p < 0.0003), but were not more likely to understand concealed allocation (p < 0.08). CONCLUSION: Subjects reported that they were satisfied with the informed consent process and their experience in a clinical trial, and that they understood trial concepts. Subjects may be able to self-assess their own level of understanding for trial concepts that intrinsically make sense within the context of their beliefs about medical care, but other trial concepts may be misunderstood/misinterpreted regardless of self-assessment of understanding or education level (i.e., concealed allocation). Subjects may prefer to believe that investigators know which treatment they are receiving, and have made a good treatment decision specific to their case, despite having being told about concealed allocation and placebo use.
Adult↗