Report of a National Conference on Donation after Cardiac Death

A national conference on organ donation after cardiac death (DCD) was convened to expand the practice of DCD in the continuum of quality end-of-life care. This national conference affirmed the ethical propriety of DCD as not violating the dead donor rule. Further, by new developments not previously reported, the conference resolved controversy regarding the period of circulatory cessation that determines death and allows administration of pre-recovery pharmacologic agents, it established conditions of DCD eligibility, it presented current data regarding the successful transplantation of organs from DCD, it proposed a new framework of data reporting regarding ischemic events, it made specific recommendations to agencies and organizations to remove barriers to DCD, it brought guidance regarding organ allocation and the process of informed consent and it set an action plan to address media issues. When a consensual decision is made to withdraw life support by the attending physician and patient or by the attending physician and a family member or surrogate (particularly in an intensive care unit), a routine opportunity for DCD should be available to honor the deceased donor's wishes in every donor service area (DSA) of the United States.     

Nosocomial and nursing home-acquired pneumonia. Recent therapeutic advances

In recent years, new broad-spectrum antibiotics have become available for the treatment of complex pneumonia. Used with care, these agents may allow effective monotherapy of difficult-to-treat pulmonary infections, with the added benefit of decreased toxicity in comparison with the more traditional multiple-drug combinations. The newer antibiotics are relatively expensive, but cost of their use can be justified by their reduced toxicity (in comparison with some antibiotic combinations) and by the avoidance of additional laboratory fees for routine drug monitoring. It is hoped that the major benefits that can accrue with proper use of the newer agents will not be outweighed by problems resulting from their indiscriminate use, such as increased bacterial resistance and exorbitant healthcare costs.     

Multiple subpial transection: a new approach to the surgical treatment of focal epilepsy

A new operative approach has been designed for the relief of medically intractable focal epilepsy. It is intended particularly to be used in those cases where the epileptogenic lesion lies in "unresectable" cortex; that is, those cerebral regions subserving speech, memory, and primary motor and sensory function. The procedure is based upon experimental evidence indicating 1) that epileptogenic discharge requires substantial side-to-side or horizontal interaction of cortical neurons, and 2) that the major functional properties of cortical tissue depend upon the vertical fiber connections of the columnar units. The technique requires severing of tangential intracortical fibers while preserving the vertical fiber connections of both incoming and outgoing nerve pathways and of the penetrating blood vessels which also have a vertical orientation. In this study, the effect of multiple subpial transection was assessed on both function and seizure control. The effect on function was reviewed in 32 cases; only 20 cases were evaluated with respect to seizure control, since a follow-up period of 5 years or more (5 to 22 years) is required before conclusions can be drawn. Multiple subpial transection was applied to the precentral gyrus in 16 cases, the postcentral gyrus in six, Broca's area in five, and Wernicke's area in five. With respect to function, the major finding was that none of the 32 patients has suffered a clinically significant behavioral deficit (although subtle deficits could be detected by careful neurological examination). Complete control of seizures has been obtained in 11 (55%) of the 20 cases evaluated. Nine patients developed recurrent seizures consequent to progressive disease unsuspected before operation (Rasmussen's encephalitis in five, tumor in three, and subacute sclerosing panencephalitis in one). In none of these cases, however, did the recurrent seizures arise in the transected zone. Thus, the results indicate that multiple subpial transection is about as effective as standard excisional therapy, and can be successfully employed when epileptogenic lesions encroach upon cortical territories, the removal of which would be functionally incapacitating.     

A six-year epidemiologic review of pneumonia in Department of Veterans Affairs facilities

OBJECTIVE: Pneumonia and acute lower respiratory infections are a major problem in the United States and worldwide. As one of the largest health care organizations in the United States, the Department of Veterans Affairs is an ideal location for an epidemiologic review of pneumonia over an extended period of time. METHODS: Data for this study were retrieved from the Department of Veterans Affairs Austin Automation Center, the central repository for patient data in the Veterans Health Administration (VHA). In addition, specific data regarding penicillin-resistant Streptococcus pneumoniae in VHA facilities were obtained from an annual electronic nationwide census. RESULTS: The case rate of pneumonias as a discharge diagnosis increased during the 6-year period. For the diagnosis group of bronchopneumonia and pneumonia with organism unspecified, the largest subset examined, total numbers and rates for this specific diagnosis increased during the study period. When fiscal year (FY)91 and FY96 were compared, rates increased for three diagnoses: overall pneumonia, pneumonia in infectious diseases classified elsewhere, and pneumococcal pneumonia. Decreases in rates occurred between FY91 and FY96 for pneumonia caused by other specified organisms and other bacterial pneumonia. The total number of discharges from VHA facilities decreased during the 6-year period. CONCLUSIONS: The numbers of episodes of bronchopneumonia and pneumonia with organism unspecified, the largest pneumonia subset, increased during the 6-year period to greater than 27,000 cases. As the number of total discharges from the VHA decreased, the combination of increasing actual numbers and decreasing discharges yielded increased rates for overall pneumonia and certain subsets. These data should be useful in developing aggressive preventive strategies.     

Improved detection of chromosome 16 rearrangements in acute myeloid leukemias using 16p and 16q specific microdissection DNA libraries

DNA libraries of the human chromosome arms 16p and 16q have been constructed by means of microdissection for the use of fluorescence in situ hybridization (FISH) analysis of rearranged chromosome 16 in acute myeloid leukemia. FISH with differently labeled chromosome 16p and 16q arm-specific libraries on normal metaphase spreads resulted in bright painting signals on both arms of chromosome 16, each stained in a different color. Hybridization on bone marrow samples of acute leukemia patients having a pericentric inversion of chromosome 16 showed on one chromosome 16 the presence of q-arm specific material on the p-arm adjacent to the centromere and vice versa, resulting in an alternating red-green-red-green colored chromosome pattern in the FISH analysis.     

Spontaneous tumor-specific humoral and cellular immune responses to NY-ESO-1 in hepatocellular carcinoma.

PURPOSE: Hepatocellular carcinoma (HCC) is the fifth most common cancer around the world. Although several therapeutic approaches for treatment of HCC are available, survival rates for HCC patients are still very poor because of inefficient treatment options. For HCC, as well as other tumors, antigen-specific immunotherapy remains a viable approach that is dependent on the definition of tumor-associated antigens. NY-ESO-1, a member of the cancer testis antigen family, is one possible candidate for a tumor-specific antigen in HCC. The aim of this study was to show the relevance of NY-ESO-1 in hepatocellular carcinoma. EXPERIMENTAL DESIGN: Sera samples from 189 HCC patients were analyzed for NY-ESO-1-specific antibodies. Forty-nine HCC patients were screened for NY-ESO-1 mRNA expression in HCC tissue. Selected patients were followed for up to 3 years to correlate their immune response with their clinical course of events. NY-ESO-1-specific CD4+ and CD8+ T-cell responses from NY-ESO-1 seropositive patients were analyzed and a NY-ESO-1+ specific cytotoxic T-cell line was generated. RESULTS: Twelve of 49 analyzed tumor samples expressed NY-ESO-1 mRNA and 23 of 189 patients showed NY-ESO-1-specific antibody responses. These humoral immune responses were accompanied by NY-ESO-1-specific functional CD4+ and CD8+ T-cell responses. Finally, NY-ESO-1 humoral responses were dependent on the presence of NY-ESO-1-expressing tumors. CONCLUSIONS: This is the first report of a spontaneous immune response in HCC patients to a known tumor-specific antigen, NY-ESO-1 protein. Our data favor the possibility of immunotherapeutic strategies for the treatment of HCC.