PROVOCATIVE EFFECTS OF THE IMMUNOSUPPRESSANTS RAPAMYCIN, TACROLIMUS, AND DEXAMETHASONE ON Pneumocystis carinii PNEUMONITIS IN CONTRAST TO THE ANTI-Pneumocystis carinii PNEUMONITIS EFFECTS OF MYCOPHENOLATE MOFETIL
Bibliographic record
Abstract
Reply to Dr. Oz et al. The suggestion by Dr. Oz and colleagues (1) that mycophenolate mofetil (MMF) prevents Pneumocystiscarinii infection echoes the intriguing finding in the U.S. Renal Transplant Study in which none of the 335 patients receiving MMF developed P. carinii pneumonitis (PCP) (2). However the incidence of PCP in the control arm of this and other control trials was so low that even a meta-analysis of 1493 patients failed to show a statistically significant benefit (3). The dose of sirolimus tested by Dr. Oz (4 mg/kg) was very high, with a mortality rate of 30% of treated rats. Early animal studies suggested that doses between 0.16 and 1.5 mg/kg prevent allograft rejection and graft-versus-host disease in the rat (4,5). Nonetheless only 29% of the surviving rats in Dr. Oz’s study became “mildly infected with PCP.” This represents a reduction by 70% of infection seen with steroids or calcineurin inhibition in this model. The authors imply that the severity of infection was also reduced. Despite this observation, our patients seemed to be at risk of opportunistic infection when converting from calcineurin inhibitors to sirolimus, and we continue to recommend prophylaxis against PCP (6). The protective effect of MMF is based on rats that received dexamethasone in their drinking water, but because the animals lost 35% of their body weight, all the steroid may not have been absorbed. We believe that caution must be used when interpreting data from animal models in the clinical context. Bioavailability and effect of immunosuppressants vary between the species and within species. Monitoring of drug levels and standardization of efficacy (such as the minimum level to prevent heterotopic heart allograft rejection) of each comparator are necessary. However, studies focusing on the toxicity of immunosuppression are important. V. C. McAlister A. S. MacDonald
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.013 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.010 | 0.014 |
| Insufficient payload (model declined to judge) | 0.004 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".