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March 29, 2001
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Diagnosing Renal-Allograft Rejection by Measurement of mRNA for Perforin and Granzyme B in Urine
Rejection is a major cause of the loss of renal allografts. The standard test for rejection is renal biopsy. In this study, levels of messenger RNA (mRNA) encoding perforin and granzyme B, two proteins produced by cytotoxic cells, were measured in the urine of renal-allograft recipients with or without an episode of acute rejection. The levels were significantly higher in the patients with an episode of acute rejection, and serial measurements of these mRNA levels could be used to predict the onset of rejection.
Perforin is thought to cause the formation of pores in the membranes of target cells, through which granzyme B enters the cells and causes fragmentation of DNA. The presence of high levels of perforin mRNA and granzyme B mRNA in the urine suggests that measurement of these substances may be clinically useful in diagnosing and even anticipating an episode of acute rejection.
Related Editorial
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Clinical Effectiveness of the Varicella Vaccine
Chickenpox was diagnosed in a total of 243 children. Of the 56 children with chickenpox who had received the varicella vaccine, 86 percent had mild disease. In contrast, of the 187 unvaccinated children with chickenpox only 48 percent had mild disease. Of the children with chickenpox, 23 percent had received the varicella vaccine, whereas 61 percent of the controls had received the vaccine (vaccine effectiveness, 85 percent). Against more severe disease, the vaccine was 97 percent effective.
The live attenuated varicella vaccine was approved for use six years ago. In this study in New Haven, Connecticut, the investigators demonstrated the effectiveness of the vaccine in clinical practice. At this time, the duration of the vaccine's effectiveness remains uncertain. However, since the varicella-zoster virus continues to circulate in the population, this can lead to natural boosting of vaccine-induced immunity.
Related Editorial
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Prevention of Depression Induced by Interferon
Interferon alfa is an effective therapy for malignant melanoma and hepatitis C. However, its use may be associated with depression. This study evaluated patients who were to receive interferon alfa for melanoma to determine whether pretreatment with the antidepressant paroxetine could reduce their risk of depression. Major depression developed significantly less frequently in patients treated with paroxetine than in those who received placebo.
Depression and neurotoxicity commonly force patients to stop taking interferon alfa. This study shows that pretreatment with an antidepressant may help to prevent these side effects. It will be important to determine whether the concurrent use of an antidepressant influences the effectiveness of interferon alfa.
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Helicobacter pylori
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Preventing Recurrent Upper Gastrointestinal Bleeding in Patients with Helicobacter pylori Infection
Many patients who have had upper gastrointestinal bleeding continue to take low-dose aspirin for cardiovascular prophylaxis or other nonsteroidal antiinflammatory drugs (NSAIDs) for musculoskeletal conditions. In these patients, it is uncertain whether infection with Helicobacter pylori is a risk factor for recurrent bleeding. In patients who continued to take low-dose aspirin, the eradication of H. pylori infection was equivalent to treatment with omeprazole in preventing further bleeding. In patients who continued to take another NSAID (naproxen), however, treatment with omeprazole was superior to the eradication of H. pylori in preventing further bleeding.
It is uncertain how to balance the potential benefits of aspirin or other NSAIDs, such as naproxen, with the increased risk of upper gastrointestinal bleeding. Since H. pylori infection is also a risk factor for bleeding, it made sense to evaluate whether the eradication of this infection could prevent recurrent bleeding in patients who were taking aspirin or naproxen. The answer is clear: eradicating H. pylori infection is equivalent to treatment with omeprazole in preventing recurrent bleeding associated with low-dose aspirin, but not with naproxen.
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