Highly diastereoselective aldol additions of a chiral ethyl ketone enolate under Lewis base catalysis.

[reaction: see text] The aldol addition of a chiral ethyl ketone enolate bearing an oxygen substituent (OTBS) at the alpha-position proceeds with high internal and relative diastereoselectivities with various achiral aldehydes in good yields. The profound influence of the resident stereogenic center allows for the use of an achiral catalyst, such as HMPA, with minor attenuation in internal stereoselectivity.

A multicenter, randomized, controlled trial of Celsior for flush and hypothermic storage of cardiac allografts.

Background: A multicenter, randomized, controlled, open-label trial was conducted to evaluate the safety and efficacy of Celsior when used for flush and hypothermic storage of donor hearts before transplantation.

Methods: Heart transplant recipients were randomized to one of two treatment groups in which donor hearts were flushed and stored in either Celsior or conventional preservation solution(s) (control). Study subjects were followed for 30 days after transplantation.

[Etiology of asthma].

Asthma is a chronic inflammatory disease of the airways which occurs in genetically predisposed individuals. This common disease has an epidemic progression in western countries. Despite the identification of several candidate genes, genetic modifications cannot explain the recent increase in asthma prevalence and severity in the last forty years.

Combined host-conditioning with CTLA4-Ig, tacrolimus, anti-lymphocyte serum, and low-dose radiation leads to stable mixed hematopoietic chimerism.

The toxic dose of irradiation required to achieve stable mixed hematopoietic chimerism is the major limitation to its clinical application in transplantation and other nonmalignant conditions such as hemoglobinopathies. This study examines the additive effect of costimulatory blockage, to our previously described tacrolimus-based conditioning regimen, in further reducing the dose of total-body irradiation to achieve stable mixed chimerism in rats. Fully mismatched, 4- to 6-week-old ACI and Wistar Furth rats were used as donors and recipients, respectively.

Phenotypic drug susceptibility testing predicts long-term virologic suppression better than treatment history in patients with human immunodeficiency virus infection.

To assess the value of phenotypic drug susceptibility testing as a predictor of antiretroviral treatment response in human immunodeficiency virus (HIV)-infected people, drug susceptibility testing was performed retrospectively on plasma samples collected at baseline in a cohort of 86 antiretroviral-experienced, HIV-infected people experiencing treatment failure and initiating a new antiretroviral treatment regimen. Two separate criteria for reduced drug susceptibility were evaluated. In multivariate analyses, phenotypic susceptibility was an independent predictor of time to treatment failure (adjusted hazards ratio [HR], 0.

Note: dissolution of aerosol particles of budesonide in Survanta, a model lung surfactant.

The effect of a pulmonary surfactant extract from bovine lung, Survanta, on the dissolution rate of aerosol particles of budesonide was determined. Aerosol particles of budesonide were generated from an ethanol solution, dried, and collected by a cascade impactor for characterization or by a liquid impinger for dissolution experiments. Powder x-ray diffraction, differential scanning calorimetry, differential thermal analysis, and scanning electron microscopy were used to characterize the aerosol particles and starting material.

FK409, a spontaneous nitric oxide releaser, attenuates allograft vasculopathy in a rat aortic transplant model.

Although systemic administration of NO donors has been shown to attenuate the development of neointimal hyperplasia in the balloon injury model, this strategy has not been tested in a model of allograft vasculopathy. In this study, we investigated the effect of FK409, a spontaneous NO releaser, on the development of allograft vasculopathy, using a rat aortic transplant model. Thoracic aortas from ACI rats were transplanted heterotopically into the abdominal aorta of Wistar-Furth rats.

Inhaled corticosteroids and Churg-Strauss syndrome: a report of five cases.

Churg-Strauss syndrome is an eosinophil-associated, small vessel granulomatous vasculitis, characterized by late onset asthma, upper airways disease, eosinophilia, and clinical manifestations of systemic vasculitis. Several cases of Churg-Strauss syndrome have been recognized in patients treated with cysteinyl leukotriene-receptor antagonists and weaned off systemic corticosteroids. These cases have led to a general warning on the possible development of Churg-Strauss syndrome after taking cysteinyl leukotriene-receptor antagonists.

Cardiac transplantation in survivors of lymphoma: a multi-institutional survey.

Background: Cardiac transplantation has been successfully performed in patients with a history of presumably cured Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). Though the risk of recurrence is a major concern, the long-term influence of prior cancer and cancer therapy on posttransplant outcome has not been previously investigated.

Methods: Questionnaires were sent to 130 cardiac transplant centers in the United States registered with the United Network for Organ Sharing.

Impact of zidovudine-based triple combination therapy on an AIDS drug assistance program.

A static deterministic model was used to estimate the effect of the shift to a triple combination therapeutic standard on the annual AIDS Drug Assistance Program (ADAP) budget, total medical care expenditures, and population health outcomes for New York (NY) state ADAP enrollees. The model used opportunistic disease incidence data from the Multicenter AIDS Cohort Study (MACS) and other studies. Costs of treating opportunistic infections (OIs) and other HIV complications with each type of therapy were derived from treatment algorithms and standard unit costs.

Effects of donor bone marrow infusion in clinical lung transplantation.

Background: We have demonstrated that donor cell chimerism is associated with a lower incidence of obliterative bronchiolitis (OB) in lung recipients, and that donor chimerism is augmented by the infusion of donor bone marrow (BM). We herein report the intermediate results of a trial combining the infusion of donor BM and lung transplantation.

Methods: Clinical and in vitro data of 26 lung recipients receiving concurrent infusion of donor bone marrow (3.

A clinical trial combining donor bone marrow infusion and heart transplantation: intermediate-term results.

Background: Donor chimerism (the presence of donor cells of bone marrow origin) is present for years after transplantation in recipients of solid organs. In lung recipients, chimerism is associated with a lower incidence of chronic rejection. To augment donor chimerism with the aim to enhance graft acceptance and to reduce immunosuppression, we initiated a trial combining infusion of donor bone marrow with heart transplantation.

Hydraulic high-pressure nebulization of solutions and dispersions for respiratory drug delivery.

The purpose of this investigation was to assess hydraulic high-pressure nebulization as a means for respiratory drug delivery. A hydraulic high-pressure nebulizer was designed and constructed. In a design study, the output efficiency and the aerosol particle size were determined for the nebulizer as a function of nozzle diameter (5, 10, and 20 microns), gas flow rate (2 and 8 l/min), applied hydraulic pressure (2200 and 4000 psig), and distance between the nozzle orifice and impaction surface (0.

Analysis of a diffusion dryer for the respiratory delivery of poorly water soluble drugs.

Purpose: The purpose of this study was to analyze a diffusion dryer as a means to remove organic solvents from aerosol particles of poorly water soluble drugs.

Methods: Aerosols of methanol, ethanol, and ethyl acetate were generated with an ultrasonic nebulizer, and inflow to outflow concentration ratio of vapor in a annular charcoal column was determined as a function of time by gas chromotography at two to four different airflow rates. In addition, the particle transmission efficiency was determined with an ethanol solution of the test compound, budesonide.

Effect of ischemic time on survival in clinical lung transplantation.

Background: While there is convincing evidence that prolonged ischemic times correlate with reduced long-term survival in heart transplantation, the effect of ischemic time on outcome in clinical lung transplantation remains controversial. To assess the effect of ischemic time on outcomes in lung transplantation, we reviewed our experience.

Methods: The study was performed by retrospective chart review.

Native heart complications after heterotopic heart transplantation: insight into the potential risk of left ventricular assist device.

Background: In heterotopic heart transplantation, the donor heart is connected parallel to the recipient's diseased heart. Recipients continue to have risks, such as arrhythmia, thromboembolism, valvular heart disease, and ischemic heart disease which can develop in the native heart. It may serve as a clinical model to study long-term pathophysiologic processes in the native heart of patients with a left ventricular assist device.

A prospective cost-consequence analysis of adding lamivudine to zidovudine-containing antiretroviral treatment regimens for HIV infection in the US.

Background: Healthcare resource use data were collected for 1 year as part of the CAESAR (Canada, Australia, Europe, South Africa) clinical trial, which evaluated the effect of adding lamivudine to treatment regimens containing zidovudine in patients with HIV infection. This study showed that lamivudine-containing regimens reduced HIV disease progression to AIDS or death, in addition to significantly reducing the number of hospital stays, unscheduled outpatient visits, and medications for HIV-related illness. Estimates of US unit costs for each healthcare service were derived from nationally representative data sources, and were used to determine the costs of treatment during the trial period for the treatment and control groups.

Synthesis and kinetics of cyclization of MHC class II-derived cyclic peptide vaccine for diabetes.

Conformationally constrained cyclic peptides are known to be better vaccines because of their ability to mimic the native structure of a protein against which an immune response is sought. To test the hypothesis of using conformationally constrained, disease-associated, MHC-derived peptides as vaccines for the prevention of type I diabetes, a 22 amino acid nonobese diabetic(NOD) mouse MHC class II-derived synthetic peptide was cyclized by the formation of end-to-end disulfide bonds and used to prevent diabetes and insulitis in NOD mice. The peptide was synthesized by Fmoc chemistry and cyclized using two methods: a commercially available cyclizing resin (Ekathiox) and air oxidation.

A partial conditioning approach to achieve mixed chimerism in the rat: depletion of host natural killer cells significantly reduces the amount of total body irradiation required for engraftment.

Background: Mixed allogeneic bone marrow chimerism induces tolerance to solid organ grafts. Although we previously reported that partially ablative conditioning with 700 cGy of total body irradiation (TBI) is sufficient to allow for bone marrow engraftment in mice, we determined that a minimum of 1000 cGy was required in the rat. Because T cells and NK cells are critical in bone marrow graft rejection, our purpose was to examine whether targeting of radioresistant NK cells and/or T cells in the recipient hematopoietic microenvironment would reduce the TBI dose required for engraftment of allogeneic rat bone marrow.

Infusion of donor leukocytes to induce tolerance in organ allograft recipients.

To further enhance chimerism, 229 primary allograft recipients have received perioperative intravenous infusion of a single dose of 3 to 6 X 10(8) unmodified donor bone marrow (BM) cells/kg body weight. In addition, 42 patients have been accrued in a concurrent protocol involving multiple (up to three) sequential perioperative infusions of 2 x 10(8) BM cells/kg/day from day 0-2 posttransplantation (PTx). Organ recipients (n = 133) for whom BM was not available were monitored as controls.

Mixed hematopoietic chimerism prevents allograft vasculopathy.

Background: Mixed hematopoietic chimerism has been shown to induce long-term acceptance of transplant organs. We determined whether mixed chimerism prevented allograft vasculopathy, using the rat aortic allograft model.

Methods: Mixed chimeras were prepared by reconstituting lethally irradiated (1100 cGy) WF rats with a mixture of T-cell depleted (TCD) syngeneic (WF) plus TCD allogeneic (ACI) bone marrow.

T-cell depletion of allogeneic bone marrow using anti-alphabetaTCR monoclonal antibody: prevention of graft-versus-host disease without affecting engraftment potential in rats.

Bone marrow chimerism may solve two major limitations in the transplantation of solid organs and cellular grafts: (1) the requirement for life-long immunosuppressive therapy, and (2) acute and chronic rejection. When untreated bone marrow is transplanted into major histocompatibility complex (MHC)-disparate rats, lethal graft-vs-host disease (GVHD) occurs in the majority of recipients. T-cell depletion using anti-CD3 and anti-CD5 monoclonal antibody (mAb) to avoid GVHD led to an increased occurrence of failure of engraftment.

The pigtail catheter for pleural drainage: a less invasive alternative to tube thoracostomy.

Background: Tube thoracostomy remains the standard of care for the treatment of pneumothoraces and simple effusions. This report describes a favorable experience with the 8.3 French pigtail catheter as a less invasive alternative to traditional chest tube insertion.