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Faced with a shortage of cadaver livers for transplants, doctors increasingly are relying on transplanting a portion of a liver from one adult to another. But it is difficult to know the risks involved as no complete listing or centralized registry exists of donor and recipient morbidity and mortality. Some experts, citing the lack of information, are calling for restrictions on which centers can perform the procedure or for government regulation.

Now, Columbia University Health Sciences researchers and colleagues have found that in the past few years transplant surgeons in the United States have been performing more adult-to-adult living donor liver transplantations and that centers that do the most of these procedures also have the lowest complication rates.

The investigators, led by Dr. Robert S. Brown, associate professor of medicine at P&S, and medical director at NewYork-Presbyterian Hospital's Center for Liver Disease and Transplantation, sent surveys to all 122 transplant programs registered in the United States to report on transplants they had performed before November 2000. Of the 84 centers that responded, 42 centers performed at least one living donor liver transplant between 1997 and 2000, for a total of 449. Of the remaining 42 centers, 32 planned to start performing the procedure within the next 12 months.

The number of adult-to-adult living donor liver transplants increased from one in 1997 to 266 in 2000. Fourteen centers had performed more than 10 such procedures during the four-year period, accounting for 362 or 80 percent of the total.

Although 65 of the 449 donors (14 percent) experienced one or more complications, such as bile leaking from the liver, centers with the highest quartile of donor complication had complications in more than 33 percent of donors. These higher complication rate centers performed fewer living donor liver transplants (an average of four) compared with the remaining programs (average of 14). However, the donor mortality rate for all centers was very low—only one donor out of 449 died (0.2 percent). The findings were published in the Feb. 27 New England Journal of Medicine.

—Matthew Dougherty

Americans in all states have the right to see their medical records, which are increasingly kept in electronic form and are accessible to physicians over the Web. But clinicians have reservations about giving patients access to electronic medical records because patients may misinterpret lab results or inundate them with questions.

In a pioneering study that examines how the clinician-patient relationship fares when patients view electronic records via the Web, Dr. James Cimino, professor of medicine and medical informatics, reports that clinicians felt access actually improved the relationship. The results were published in the Dec. 18 International Journal of Medical Informatics.

In the study, Dr. Cimino and his colleagues designed a secure Web-based system for patients to access their data in WebCIS, NewYork-Presbyterian Hospital's medical records database. Three physicians replied to a letter soliciting physician participants. The three physicians then recommended 13 patients, 11 of whom completed the study. The researcher's system provided the patients with educational materials that would help them interpret the raw medical data within the record. The researchers then monitored which parts of the record the 11 patients viewed and, after nine months, interviewed the patients and their physicians.

The researchers found that patients almost exclusively used the system to access their lab results or to enter their own data, such as blood sugar or weight. In interviews, the patients said they had no complaints with the system and said knowing lab test results before seeing their doctor was helpful. The doctors said communication with their patients improved.

Though no adverse events occurred during the study, Dr. Cimino says the system would need enhanced educational materials to work with patient populations who may not be as sophisticated as the study subjects.

—Susan Conova

The neurotransmitter glutamate helps the brain function normally but when it stays around too long, it overstimulates and kills neurons by a process called excitotoxicity. Recent research has found excess glutamate associated with neuronal death in a range of neurological disorders, including stroke, temporal lobe epilepsy, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), Huntington's disease, HIV-1-associated dementia, and growth of malignant gliomas.

It has been unclear to scientists, however, how glutamate transport is regulated. Now, research by Columbia University Health Sciences researchers and colleagues indicates that glutamate levels may be regulated by transcription of at least one gene that controls its transport inside and outside of astrocytes, a type of central nervous system cell.

The researchers, led by Dr. Paul B. Fisher, professor of clinical pathology at P&S and director of neuro-oncology research, identified and cloned the promoter, a region of a DNA sequence that regulates expression of a gene for the major glutamate transporter in the central nervous system called excitatory amino acid transporter-2 (EAAT2). Before the promoter was identified, the molecular basis of how glutamate transport was regulated was unknown. Cloning the promoter, which was done using human fetal astrocyte cells, was difficult and time consuming because of the structure of the EAAT2 gene, says Dr. Fisher, who is also the Michael and Stella Chernow Urological Cancer Research Scientist.

The investigators also demonstrated that the EAAT2 promoter displays elevated expression in astrocytes. The investigators tested a variety of regulators of EAAT2 transport and found that the regulators alter EAAT2 transcription, promoter activity, mRNA, protein and glutamate levels in astrocytes. These results imply that transcriptional processes can regulate EAAT2 expression.

Now that the promoter's identity is known, researchers should be able to develop high-throughput assays to discover drugs that target the promoter as a way to treat, prevent, or even cure some neurodegenerative diseases, Dr. Fisher says.

Additional authors of the paper are Dr. Zao-zhong Su, research scientist at P&S; Dr. Magdalena Leszczyniecka, formerly a graduate student in Dr. Fisher's lab and now at Novartis Pharmaceuticals; Dr. Dong-chul Kang, associate research scientist at P&S; Dr. Devanand Sarkar, postdoctoral research scientist at P&S; Dr. David J. Volsky, professor of clinical pathology at P&S; and Wei Chao, research associate. The research was supported by the National Institutes of Health's National Institute of Neurological Disorders and Stroke and published in the Feb. 18 Proceedings of the National Academy of Science.

—Matthew Dougherty


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