Improving how we evaluate the toxicity of approved drugs.
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Biomedical subjects
Publications and source records attributed to Marcus M Reidenberg.
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Concern of physicians about being disciplined for prescribing opioids for patients in pain is one cause for undertreatment of pain. This study was done to assess the actual risk of being disciplined by state medical boards. A review of records of actions by the New York State Board for Professional Medical Misconduct for 3 years and of all medical boards in the United States for 9 months was done to determine this risk. New York State, with 7.8% of U.S. physicians, had 10 physicians disciplined annually related to overprescribing opioids, while the total for the entire U.S. was 120 physicians annually. Most physicians disciplined had multiple violations in addition to overprescribing controlled substances. In the national sample, 43% were prescribing for themselves or for nonpatients, 12% prescribed for addicts without addressing the patients' problems of addiction, 42% had inadequate records, 19% prescribed without indication for opioids, 13% were incompetent in additional ways, and 8% were having sexual activity with patients. Not a single physician, for whom information was available, was disciplined solely for overprescribing opioids. The actual risk of an American physician being disciplined by a state medical board for treating a real patient with opioids for a painful medical condition is virtually nonexistent.
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A grand mal seizure is an unexpected, rare adverse event in a child receiving eye drops to dilate the pupils for an eye examination. A case is reported of a convulsion in a 23-month-old boy after he received Cyclogyl (cyclopentolate) and Neo-Synephrine (phenylephrine) eye drops before ophthalmoscopy. His serum sodium was 125 mEq/L, and he had low plasma pseudocholinesterase activity. Children exposed to organophosphate insecticides and other pseudocholinesterase inhibitors may be at risk for cyclopentolate toxicity.
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One of the important causes of bias in the medical literature is failure to publish data because it is "negative". Usually, this is due to failure to write a manuscript and submit it for publication. Since publication is an essential part of research and patients have been recruited into a study in the belief that they are participating in medical research, there is an ethical commitment to publish the observations made on volunteer subjects. This can be enforced by ethical committees if they refuse to approve studies of investigators and sponsors who have failed to publish earlier studies.
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Gossypol, a polyphenolic, aldehyde-containing constituent of cottonseed, produced partial responses (>50% reduction in tumor size) in some patients with advanced cancer and suppressed sperm as an antifertility agent for men. This action in vivo and its novel side effect profile suggest a specific mechanism of the action of gossypol. Using the random homozygous knockout approach of Li and Cohen (1), we developed a cell line resistant to killing by gossypol, but sensitive to methotrexate and doxorubicin. It showed stereospecific resistance to killing by (-) gossypol (ED(50) 4.9 microM) compared with wild type (ED(50) 2.0 microM). The resistant and wild-type cells were equally sensitive to (+) gossypol (ED(50) 8.8 and 8.4 microM, respectively), methotrexate, and doxyrubicin. We conclude that gossypol affects cells by a stereospecific pathway for (-) gossypol, possibly related to its selective effects, and a nonstereospecific pathway for (+) gossypol and higher concentrations of (-) gossypol. Further knowledge about the stereospecific pathway may lead to new therapeutic drugs.