The ethical complexities of online organ solicitation via donor-patient websites: avoiding the "beauty contest".

The proliferation of the Internet has spurred the creation of websites dedicated to facilitating living directed organ donations. We argue that such sites potentially devolve into "beauty contests" where patients in need are evaluated on the basis of their personal appearance and biography-variables which should have no relevance to organ allocation. Altruism should be the guiding motivation for all donations, and when it does, there is no place for a beauty contest. The power of the Internet is optimally used when it facilitates Good Samaritan donations-donations to any stranger, rather than handpicked ones. Social networking sites which aim to match potential donors and patients should mask personal identifying information, allowing the ethical principles of altruism and justice to guide organ allocation.

Solution phase synthesis of libraries of variably substituted olefin scaffolds: a library of allylic amines.

The synthesis of allylic amine libraries derived from olefin templates is described. The two-step, solution phase reaction sequence consists of amination of the template followed by Suzuki coupling and expedited purification via ion exchange chromatography. The methodology has been used to synthesize a 1344-member allylic amine library.

Practices in forensic neuropsychology: perspectives of neuropsychologists and trial attorneys.

Members of the National Academy of Neuropsychology and the Association of Trial Lawyers of America were surveyed concerning current practices in forensic neuropsychology. The majority of neuropsychologists and attorneys reported that attorneys never observe neuropsychological testing. Attorneys reported receiving raw data in almost all of their brain injury cases, but neuropsychologists reported that they produce raw data in only a minority of their forensic cases. Similarly, fewer neuropsychologists than attorneys acknowledged that they are asked to provide information to assist the lawyer in preparing for the cross-examination of the opposition's expert or to prepare the plaintiff for the opposition's evaluation. Lawyers typically spend up to an hour preparing their clients for neuropsychological evaluations and commonly cover test content, detection of malingering, and brain injury symptoms. Other topics addressed include attorney influence on findings, fees and billing, board certification, use of technicians, and methods used to generate referrals or locate experts. Areas of agreement and divergence between the groups were identified and ethical issues raised by identified practices were examined.

Synthesis of stereodefined polysubstituted olefins. 1. Sequential intermolecular reactions involving selective, stepwise insertion of Pd(0) into allylic and vinylic halide bonds. The stereoselective synthesis of disubstituted olefins.

Palladium-catalyzed allylic substitution and cross-coupling reactions have been combined into a sequential procedure to provide a range of disubstituted olefin products starting from two-, three-, and four-carbon common olefin templates. Diverse application of this template strategy is demonstrated in a variety of model studies and in a parallel synthesis (combinatorial) approach to prepare an allylic amine molecular library. An approach toward the preparation of astaxanthin beta-D-diglucoside, an interesting antioxidant whose total synthesis has yet to be reported, using the olefin-template approach is also discussed.

Intensive medical management of ureteral calculi.

OBJECTIVES: To compare two treatment regimens in patients with ureteral calculi. One regimen (control arm) used routine drugs, and the second regimen (treatment arm) used the same routine drugs plus uncommonly used drugs. METHODS: Between February and October 1998, 70 consecutive patients were evaluated for symptomatic ureteral calculi. Thirty-five patients were randomized to a control arm and received ketorolac, oxycodone, and acetaminophen combination tablets and prochlorperazine suppositories. Thirty-five patients were randomized to the treatment arm and received the same medications plus nifedipine XL, prednisone, and trimethoprim/sulfa combination tablets and plain acetaminophen. Stone passage rates, work days lost, emergency room visits, surgical interventions, and possible side effects of the drugs were recorded. RESULTS: The treatment arm (addition of nifedipine XL, prednisone, trimethoprim/sulfa, and plain acetaminophen) had higher (86% versus 56%) stone passage rates and fewer lost work days (mean 1.76 versus 4.9), emergency room visits (1 versus 4), and surgical interventions (2 versus 15). Both arms exhibited similar potential drug side effects. CONCLUSIONS: The addition of a calcium channel blocking agent, steroids, antibiotics, and more acetaminophen effected a higher stone passage rate and fewer lost work days, emergency room visits, and surgical interventions.

Selection criteria for clinical neuropsychology internships.

Criteria used in the evaluation and selection of applicants for clinical neuropsychology internships were identified by a survey of the programs listed in The Clinical Neuropsychologist. Neuropsychologists from 40 programs replied to the survey, yielding an 80% response rate. Clinical experience in neuropsychological assessment, specialization in clinical neuropsychology during graduate training, personal interview, and letters of recommendation were reported to be the most salient selection criteria. Practica that provide experience with flexible batteries at university-affiliated medical centers and doctoral curricula that follow INS/APA Division 40 guidelines, with teaching and supervision provided by neuropsychologists were preferred prerequisites to internship. Selection criteria reflect a vertically integrated model of education and training in accordance with the Houston Conference model.

Airbag mediated death of a two-year-old child wearing a shoulder/lap belt.

Airbag injuries have resulted in the deaths of several infants and small children, and such deaths are generally associated with rearward-facing infant seats or unrestrained children in front passenger seats of cars equipped with airbags. An airbag can also cause death in a small child wearing a shoulder/lap belt, however, as this case report illustrates. A two-year-old female was involved in a low-speed collision while riding in the front passenger seat of a dual-airbag-equipped automobile. Secondary impact with the airbag caused catastrophic occipitoatlantoaxial disarticulation with traumatic spinal cord separation, thermal injury and abrasions of the right forearm and distinctive patterned abrasions of the face. The possibility of airbag injury should be considered in all low-speed traffic fatalities, and the confirmatory injuries sought at postmortem examination.

A20 inhibits NF-kappaB activation in endothelial cells without sensitizing to tumor necrosis factor-mediated apoptosis.

Expression of the NF-kappaB-dependent gene A20 in endothelial cells (EC) inhibits tumor necrosis factor (TNF)-mediated apoptosis in the presence of cycloheximide and acts upstream of IkappaBalpha degradation to block activation of NF-kappaB. Although inhibition of NF-kappaB by IkappaBalpha renders cells susceptible to TNF-induced apoptosis, we show that when A20 and IkappaBalpha are coexpressed, the effect of A20 predominates in that EC are rescued from TNF-mediated apoptosis. These findings place A20 in the category of "protective" genes that are induced in response to inflammatory stimuli to protect EC from unfettered activation and from undergoing apoptosis even when NF-kappaB is blocked. From a therapeutic perspective, genetic engineering of EC to express an NF-kappaB inhibitor such as A20 offers the mean of achieving an anti-inflammatory effect without sensitizing the cells to TNF-mediated apoptosis.

A20 blocks endothelial cell activation through a NF-kappaB-dependent mechanism.

The A20 gene product is a novel zinc finger protein originally described as a tumor necrosis factor alpha (TNF)-inducible early response gene in human umbilical vein endothelial cells (HUVEC). Its described function is to block TNF-induced apoptosis in fibroblasts and B lymphocytes, but more recently it has also been shown to play a role in lymphoid cell maturation. The mechanism of action of A20 is unknown. The aim of our study was to assess the effect of A20 upon endothelial cell activation. By transfecting bovine aortic endothelial cells (BAEC) with A20 as well as reporter constructs consisting of the promoters of genes known to be up-regulated during endothelial cell activation, i.e. E-selectin, interleukin (IL)-8, tissue factor (TF), and inhibitor of nuclear factor kappaBalpha (IkappaBalpha), we demonstrate that A20 expression inhibits gene up-regulation associated with TNF, lipopolysaccharide (LPS), phorbol 12-myristate 13-acetate (PMA), and hydrogen peroxide (H2O2)-induced endothelial cell (EC) activation. The mechanism of action of A20 is in part, or totally, due to the blockade of nuclear factor kappaB (NF-kappaB), as shown by its ability to suppress the activity of a NF-kappaB reporter. This effect is specific, as A20 does not block a noninducible, constitutively expressed reporter, Rous sarcoma virus-luciferase (RSV-LUC); nor does it block the c-Tat-inducible, NF-kappaB-independent reporter, human immunodeficiency virus-chloramphenicol acetyltransferase (HIV-CAT). How A20 blocks NF-kappaB is unclear, although we demonstrate that it does not affect p65 (RelA)-mediated gene transactivation. The inhibition of endothelial cell activation by A20 is a novel function for A20.

Inhibition of NF-kappa B by pyrrolidine dithiocarbamate blocks endothelial cell activation.

Endothelial cell activation is achieved by the rapid, protein synthesis-independent induction of a characteristic set of genes. Because of the abundance of binding sites for the transcription factor NF-kappa B in the regulatory region of the aforementioned genes, we hypothesized that this factor might play a key role. Reactive oxygen intermediates act as second messengers in the activation of NF-kappa B. We have used the antioxidant pyrrolidine dithiocarbamate to analyze the effect of NF-kappa B inhibition on TNF alpha-induced EC activation in vitro. We show that pyrrolidine dithiocarbamate strongly reduces the TNF alpha-mediated induction of E-selectin, VCAM-1, ICAM-1, PAI-1, tissue factor, IL-8 and I kappa B-alpha. We present evidence identifying NF-kappa B as a central of EC activation. Therefore, this factor may represent a prime target for therapeutic intervention in pathologic conditions associated with EC activation such as allo- and xenograft rejection, atherosclerosis, ischemic reperfusion injury and vasculitis.

Eccrine squamous syringometaplasia. A cutaneous sweat gland reaction in the histologic spectrum of 'chemotherapy-associated eccrine hidradenitis' and 'neutrophilic eccrine hidradenitis'.

A 31-year-old Hispanic man presented in the pancytopenic phase of acute myelocytic leukemia and was treated with the chemotherapeutic agents mitoxantrone and cytarabine. After 5 days, an erythematous, blanching, papular, crusted eruption developed on his forehead, chest, and legs. Some lesions showed confluence and all were at the same developmental stage. Clinical diagnoses included necrotizing vasculitis and sepsis. A biopsy specimen revealed widespread noninflammatory syringometaplasia of eccrine ducts. Well-developed intercellular bridges and eosinophilic cytoplasm were seen within the metaplastic cells; apoptoses and occasional mitoses were present. This process is distinct and probably occurred secondary to direct toxic injury from the chemotherapeutic drugs. Because similar changes have occurred in patients with neutrophilic eccrine hidradenitis, we believe our patient represents an example of the noninflammatory end of the spectrum of chemotherapeutic eccrine gland reactions.

Comparative studies on human skin fibroblasts: life span and lipid metabolism in medium containing fetal bovine or human serum.

Three strains of human skin fibroblasts were cultivated in nutrient medium supplemented either with human serum or fetal bovine serum, and growth and lipid synthesis were compared. Rates of cellular growth were similar in both kinds of medium, but the replicative life spans of all three strains were curtailed significantly in human-serum medium. Incorporation of label into the major classes of neutral lipids from [14C]acetate and 3H2O was increased also in human-serum medium. Since human serum contained higher concentrations of cholesterol known to reduce endogenous cholesterol synthesis, these results were unexpected. Nonlipid factors in human serum may account for the shortened cellular life spans and increased lipogenesis and perhaps for the potential to develop atherosclerosis.