Life-threatening coagulopathy associated with use of Campath (alemtuzumab) in maintenance steroid-free renal transplant given before surgery.

We report a case in which an alarming coagulopathy occurred during the operation in a patient receiving a kidney from his spouse. Campath was used for induction of immunosuppression immediately before surgery. There was catastrophic intra-abdominal bleeding associated with severe hypotension, respiratory failure, prolonged partial thrombin time (PTT), normal prothrombin time (PT) and absence of signs of disseminated intravascular coagulation.

Phase II trial of sequential paclitaxel and 1 h infusion of bryostatin-1 in patients with advanced esophageal cancer.

Background: We sought to determine the response rate and toxicity profile of sequential paclitaxel and bryostatin-1, a novel, selective inhibitor of protein kinase C, in patients with advanced esophageal cancer.

Patients And Methods: Patients with advanced esophageal and gastroesophageal junction cancer were enrolled. All gave informed consent.

Behind the scenes of a small RNA gene-silencing pathway.

RNA interference (RNAi) is a sequence-specific gene-silencing phenomenon mediated by double-stranded RNA. RNAi is made possible through the activity of an evolutionarily conserved RNA-protein machinery that is utilized by microRNAs (miRNAs), endogenously produced 21- to 23-nucleotide noncoding RNAs. As RNA-based therapeutics come of age, understanding the miRNA pathway and the mechanism of posttranscriptional gene silencing is paramount.

Interleukin-12 regulates natural killer cell-dependent Propionibacterium acnes-primed, lipopolysaccharide-induced liver injury.

Aim: Interleukin (IL)-12, produced primarily by macrophage/monocytes, modulates mature T and natural killer (NK) cell functions, including cytotoxicity and cytokine production.

Methods: To determine the role of IL-12 in Propionibacterium acnes (P. acnes)-primed, lipopolysaccharide (LPS)-induced liver injury, mice were injected with an anti-IL-12 monoclonal antibody (mAb) 1 and 2 days before P.

Frequency-swept ultrasound-modulated optical tomography of scattering media.

A novel frequency-swept ultrasound-modulated optical tomography technique was developed to image scattering media. A frequency-swept ultrasonic wave was used to modulate the laser light passing through a scattering medium. The modulated light was received by an optical detector and was heterodyned with a reference frequency sweep.

Small-cell carcinoma of the esophagus and gastroesophageal junction: review of the Memorial Sloan-Kettering experience.

Background: Esophageal small-cell carcinoma (SCC) is rare, highly malignant and the optimal treatment approach has not been defined.

Patients And Methods: We report the largest single-institution retrospective review of patients with esophageal and gastroesophageal (GE) junction SCC.

Results: Twenty-five patients were identified, with complete records available for 22.

Esophageal cancer: adjuvant therapy.

In the United States, esophageal cancer is an uncommon but aggressive malignancy. Prior research has focused on the incorporation of chemotherapy and radiotherapy in both the pre- and postoperative setting. Both squamous cell and adenocarcinoma histologies have been treated in trials, with adenocarcinoma now the predominant histology seen in the United States.

(S)-1-((S)-2-{[1-(4-amino-3-chloro-phenyl)-methanoyl]-amino}-3,3-dimethyl-butanoyl)-pyrrolidine-2-carboxylic acid ((2R,3S)-2-ethoxy-5-oxo-tetrahydro-furan-3-yl)-amide (VX-765), an orally available selective interleukin (IL)-converting enzyme/caspase-1 inhibitor, exhibits potent anti-inflammatory activities by inhibiting the release of IL-1beta and IL-18.

(S)-1-((S)-2-{[1-(4-amino-3-chloro-phenyl)-methanoyl]-amino}-3,3-dimethyl-butanoyl)-pyrrolidine-2-carboxylic acid ((2R,3S)-2-ethoxy-5-oxo-tetrahydro-furan-3-yl)-amide (VX-765) is an orally absorbed prodrug of (S)-3-({1-[(S)-1-((S)-2-{[1-(4-amino-3-chlorophenyl)-methanoyl]-amino}-3,3-dimethyl-butanoyl)-pyrrolidin-2yl]-methanoyl}-amino)-4-oxo-butyric acid (VRT-043198), a potent and selective inhibitor of interleukin-converting enzyme/caspase-1 subfamily caspases. VRT-043198 exhibits 100- to 10,000-fold selectivity against other caspase-3 and -6 to -9. The therapeutic potential of VX-765 was assessed by determining the effects of VRT-043198 on cytokine release by monocytes in vitro and of orally administered VX-765 in several animal models in vivo.

Combined photoacoustic and molecular fluorescence imaging in vivo.

Because of the overwhelming scattering of light in biological tissues, the spatial resolution and imaging depth of conventional fluorescent imaging is unsatisfactory. Therefore, we present a dual modality imaging technique by combining fluorescence imaging with high-resolution noninvasive photoacoustic tomography (PAT) for the study of an animal tumor model. PAT provides high-resolution structural images of tumor angiogenesis, and fluorescence imaging offers high sensitivity to molecular probes for tumor detection.

High-resolution ultrasound-aided biophotonic imaging.

Optical contrast is sensitive to functional parameters, including the oxygen saturation and total concentration of hemoglobin, in biological tissues. However, due to the overwhelming scattering encountered by light in tissues, traditional optical modalities cannot provide satisfactory spatial resolution beyond the ballistic (a few hundred microns) and quasiballistic (1-2 mm) regimes. Photoacoustic tomography is based on the high optical contrast yet utilizing the high ultrasonic resolution.

Tolerance of the cervical spine to eccentric axial compression.

Cervical spine injury resulting from compressive impact loading is a particularly devastating musculoskeletal injury due to the frequency of neurologic involvement. The objective of this research was to investigate the effect of axial eccentricity on the tolerance of the cervical spine. Two functional spinal unit segments (3 adjacent vertebra and their intervening discs and soft-tissues) were dissected from the lower cervical spine of twenty-four human cadaver cervical spines and randomly assigned to one of three loading groups.

Compressive tolerance of the maturing cervical spine.

While a number of experiments have reported injury thresholds for the adult cervical spine in compression, the compressive failure tolerance of the child spine has not been characterized. In order to develop useful safety measures for children, the biomechanical effects of maturation must be evaluated. Hence, this study examined the effects of spinal development on the compressive mechanics of the cervical spine.

Inactivation of caspase-1 in rodent brain: a novel anticonvulsive strategy.

Purpose: Cytokines and related inflammatory mediators are rapidly synthesized in the brain during seizures. We previously found that intracerebral administration of interleukin-1 (IL-1)-beta has proconvulsant effects, whereas its endogenous receptor antagonist (IL-1Ra) mediates potent anticonvulsant actions in various models of limbic seizures. In this study, we investigated whether seizures can be effectively inhibited by blocking the brain production of IL-1beta, by using selective inhibitors of interleukin-converting enzyme (ICE/caspase-1) or through caspase-1 gene deletion.

Starting low but ending high: a reversal of the anchoring effect in auctions.

Counter to the "start high, end high" effect of anchors in individual judgments and dyadic negotiations, 6 studies using a diverse set of methodologies document how and why, in the social setting of auctions, lower starting prices result in higher final prices. Three processes contribute to this effect. First, lower starting prices reduce barriers to entry, which increase traffic and generate higher final prices.

Noninvasive imaging of hemoglobin concentration and oxygenation in the rat brain using high-resolution photoacoustic tomography.

Simultaneous transcranial imaging of two functional parameters, the total concentration of hemoglobin and the hemoglobin oxygen saturation, in the rat brain in vivo is realized noninvasively using laser-based photoacoustic tomography (PAT). As in optical diffusion spectroscopy, PAT can assess the optical absorption of endogenous chromophores, e.g.

Thermoacoustic and photoacoustic tomography of thick biological tissues toward breast imaging.

Microwave-based thermoacoustic tomography (TAT) and laser-based photoacoustic tomography (PAT) in a circular scanning configuration were both developed to image deeply seated lesions and objects in biological tissues. Because malignant breast tissue absorbs microwaves more strongly than benign breast tissue, cancers were imaged with good spatial resolution and contrast by TAT in human breast mastectomy specimens. Based on the intrinsic optical contrast between blood and chicken breast muscle, an embedded blood object that was 5 cm deep in the tissue was also detected using PAT at a wavelength of 1064 nm.

The persistence of regulatory cells developing after rat spontaneous liver acceptance.

Background: We have previously reported that the spontaneous acceptance of Lewis (LEW, RT1(l)) to Dark Agouti (DA, RT1(a)) rat orthotopic liver transplant (OLT) is eliminated by donor gamma-irradiation. The acceptance of the irradiated LEW liver is also reestablished in a naïve rat after the adoptive transfer of T regulatory (T-reg) cells from a LEW to a DA liver-tolerant long-term (>60 days) survivor (LTS) into a naïve DA rat. However, little is known about the growth conditions required to maintain T-reg function.

Infectious tolerance develops after intrathymic alloantigen-induced acceptance of rat heart allografts can be adoptively transferred.

Background: We have shown that intrathymic (IT) injection of alloantigen with antirat lymphocyte serum (ALS) treatment can induce donor-specific allograft acceptance. The purpose of this study was to investigate whether T-regulatory (T-reg) cells play a role in the maintenance of donor-specific heart graft tolerance that develops after IT injection of Lewis (LEW, RT1(l)) alloantigen into a Dark Agouti (DA, RT1(a)).

Methods: Naïve DA rats were injected IT with 2.

Deeply penetrating photoacoustic tomography in biological tissues enhanced with an optical contrast agent.

Photoacoustic tomography (PAT) in a circular scanning configuration was developed to image deeply embedded optical heterogeneity in biological tissues. While the optical penetration was maximized with near-infrared laser pulses of 800-nm wavelength, the optical contrast was enhanced by Indocyanine Green (ICG) dye whose absorption peak matched the laser wavelength. This optimized PAT was able to image objects embedded at depths of as much as 5.

Imaging of tumor angiogenesis in rat brains in vivo by photoacoustic tomography.

Green laser pulses at a wavelength of 532 nm from a Q-switched Nd:YAG laser were employed as irradiation sources for photoacoustic tomography (PAT). The vascular structure of the brain was imaged clearly, with optimal contrast, because blood has strong absorption near this wavelength. The photoacoustic images of rat brain tumors in this study clearly reveal the angiogenesis that is associated with tumors.

Half-time image reconstruction in thermoacoustic tomography.

Thermoacoustic tomography (TAT) is an emerging imaging technique with great potential for a wide range of biomedical imaging applications. In this paper, we propose and investigate reconstruction approaches for TAT that are based on the half-time reflectivity tomography paradigm. We reveal that half-time reconstruction approaches permit for the explicit control of statistically complementary information that can result in the optimal reduction of image variances.

Long lives, short indications. The case for removable inferior cava filters.

Vena cava filters have been in use for decades to prevent pulmonary embolization from deep venous thrombosis. These filters have been shown to be effective, with fairly low rates of filter migration, fracture and thrombosis. However considering that filters remain in situ for the life of the patient and that studies do not show increased longevity in patients with filters, any complications from filters are significant concerns.

Regulatory cells develop after the spontaneous acceptance of rat liver allografts.

Background: After donor-specific transfusion, tolerance to heart transplants is serially passed to naive rats by the adoptive transfer of long-term survivor (LTS)-tolerant splenocytes (SC). We examined whether regulatory cells similarly develop after the spontaneously accepted Lewis (LEW) to Dark Agouti (DA) liver transplants.

Methods: SC from a LTS DA rat with a LEW liver were adoptively transferred to a naive DA 1 day before transplantation of an irradiated (1000 rad) LEW liver.