Primary arteriovenous fistula between common iliac vessels: ultrasound, computer tomographic, and angiographic findings--a case report

A giant aneurysm of the right common iliac artery presenting with an arteriovenous fistula (AVF) between the iliac artery and iliac vein and deep venous thrombosis of the right lower extremity is reported. The clinical signs and the radiologic and surgical management of the condition are discussed. In addition a brief review of the literature is given.     

Chronic thromboembolic occlusion in the adult can mimic pulmonary artery agenesis

In the first 100 patients operated on for C T-E PH, three were referred with the diagnosis of UPAA having been made elsewhere. We found that many features of these two conditions are so similar that differential diagnosis is very difficult. Shared features may include findings on chest x-ray film, pulmonary angiography, CT scan and MRI studies. Since the two conditions vary substantially with respect to the methods of potential surgical correction, recognition of this possible differential diagnostic dilemma is important.     

Functional development of the visual system in normal and protein-deprived rats. IV. Latencies in the specific visual pathway of adult rats

It was recently shown that an increase in latency of the cortical visual evoked response (VER) seen in young malnourished animals persists in adult rats given a low protein diet. In the present paper the VER latencies of the specific visual pathway were measured in order to establish the level at which the latency increase occurs in protein-deprived rats. The VER in the dorsal lateral geniculate nucleus (dLGN) showed no significant differences to onset or peak latencies between control (C) and the protein-deprived (PD) rats. The dLGN activity was higher in C rats than in PD rats. Late components differed in median values between the two groups, but the individual variations were large. Generally, the VER of the dLGN in PD rats was more stereotype compared with the C rats. Intracortical VER at a depth of 0.4-0.5 mm showed a small negative component of short onset latency in both C and PD rats. This component preceded the onset of the initial positivity recorded from the cortical surface by 1-2 ms in C rats and by 3-6 ms in PD rats. Following electrical stimulation of the dLGN, no differences in onset latency of the first cortical activity (monosynaptic response) were recorded between C and PD rats, whereas later activity was significantly delayed in PD compared with C rats. The laminar potential pattern was less distinct in PD compared with C rats, and the late components of the evoked response from deep cortical layers were markedly attenuated or lacking.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fate of micelles and quantum dots in cells.

Micelles and quantum dots have been used as experimental drug delivery systems and imaging tools both in vitro and in vivo. Investigations of their fate at the subcellular level require different surface-core modifications. Among the most common modifications are those with fluorescent probes, dense-core metals or radionucleids. Cellular fate of several fluorescent probes incorporated into poly(caprolactone)-b-copolymer micelles (PCL-b-PEO) was followed by confocal microscopy, and colloidal gold incorporated in poly 4-vinyl pyridine-PEO micelles were developed to explore micelle fate by electron microscopy. More recently, we have examined quantum dots (QDs) as the next-generation-labels for cells and nanoparticulate drug carriers amenable both to confocal and electron microscopic analyses. Effects of QDs at the cellular and subcellular levels and their integrity were studied. Results from different studies suggest that size, charge and surface manipulations of QDs may play a role in their subcellular distribution. Examples of pharmacological agents incorporated into block copolymer micelles, administered or attached to QD surfaces show how the final biological outcome (e.g. cell death, proliferation or differentiation) depends on physical properties of these nanoparticles.     

Evidence of lowest brain penetration of an antiemetic drug, metopimazine, compared to domperidone, metoclopramide and chlorpromazine, using an in vitro model of the blood-brain barrier.

PURPOSE: The objective of the current study was to determine the ability of some antiemetic compounds to cross the blood-brain barrier (BBB) and thereby to determine possible side effects of compounds for the central nervous system (CNS). METHODS: We compared the brain penetration of some antiemetic compounds using an in vitro BBB model consisting in brain capillary endothelial cells co-cultured with primary rat glial cells. RESULTS: This study clearly demonstrated that the metopimazine metabolite, metopimazine acid, has a very low brain penetration, lower than metopimazine and even less than the other antiemetic compounds tested in this study. CONCLUSIONS: The poor brain penetration of metopimazine acid, metopimazine biodisponible form, seems very likely related to the clinically observed difference in therapeutic and safety profile.     

Relationship of MAO-A promoter (u-VNTR) and COMT (V158M) gene polymorphisms to CSF monoamine metabolites levels in a psychiatric sample of caucasians: A preliminary report.

Monoamine oxidase A gene promoter (MAOA-uVNTR) and catechol-O-methyltransferase V158M (COMT-V158M) gene functional polymorphisms are reported to be associated with impulsive-aggression, but a biological intermediate effect remains to be determined. This study assessed the association of these polymorphisms with cerebrospinal fluid (CSF) monoamine metabolites as endophenotypes. Ninety-eight Caucasian psychiatric subjects were assessed for Axis I and II diagnosis. Subjects were genotyped for the functional polymorphisms, MAOA-uVNTR and COMT-V158M. CSF was obtained by lumbar puncture. Relationships of the two polymorphism to monoamine metabolites: HVA, 5-HIAA, and MHPG were examined. The higher-expressing MAOA-uVNTR genotype was associated with higher CSF-HVA levels in males only (n = 46) (195.80 pmol/ml, SD = 61.64 vs. 161.13, SD = 50.23, respectively; P = 0.042). No association was found with diagnosis. COMT-V158M had no association with CSF monoamine metabolites. The association of MAOA-uVNTR with dopaminergic activity in males is a preliminary finding that needs to be replicated in a larger sample of Caucasian males and relationships sought with clinical phenotypes. This article contains supplementary material, which may be viewed at the American Journal of Medical Genetics website at http://www.interscience.wiley.com/jpages/0148-7299:1/suppmat/index.html.     

Combining Vaccines with Conventional Therapies for Cancer

Preclinical and clinical investigations currently underway are employing novel strategies for combining vaccines with conventional and experimental anticancer therapies. To date, the FDA has not approved a therapeutic cancer vaccine. However, the results of recent investigations suggest an increasing role for vaccines in new models of combination therapy for many types of cancer. This article reviews and discusses therapeutic cancer strategies that employ vaccines in combination with local radiation, chemotherapy, hormone therapy, and anti-CTLA-4 mAb. Preclinical studies have shown that certain anticancer agents have immune modulatory effects that result in up-regulation of surface expression of MHC molecules, tumor-associated antigens, or Fas on malignant cells, rendering them more susceptible to immune destruction. Preliminary results of clinical studies using combination strategies have demonstrated a postvaccination antigen cascade, prolonged time to disease progression, and improved overall survival. Several larger randomized trials are ongoing, and more are required to support these findings.     

A novel assay for factor XIII based on cross-linking of synthetic peptides: analysis of different substrates.

A novel assay for factor XIII is described that utilizes exclusively small synthetic peptides as substrates for the cross-linking reaction catalyzed by activated factor XIII (FXIIIa). The acyl donor substrate (selection peptide) is immobilized on a microplate via biotin while the acyl acceptor substrate (detection peptide) is labeled with the fluorochrome Oregon green to allow sensitive detection without the need for secondary enzyme systems for signal amplification. Starting with an amino acid sequence from the fibrin gamma-chain (GQQHHLGGAKQAGDV) as a prototype peptide, the influence of amino acid exchanges were investigated with respect to their impact on the FXIIIa-catalyzed reaction. It was found that FXIIIa readily accepts a broad range of substrate peptides, with a proline neighboring the essential lysine having the most detrimental effect. The assay appears to be valuable for the molecular characterization of factor XIII and may be used for a deeper investigation into the substrate requirements of this final enzyme of wound repair, and eventually also for the characterization of other transglutaminases.     

First-pass effects of verapamil on the intestinal absorption and liver disposition of fexofenadine in the porcine model.

The aim of this study in pigs was to investigate the local pharmacokinetics of fexofenadine in the intestine and liver by using the pig as a model for drug transport in the entero-hepatobiliary system. A parallel group design included seven pigs (10-12 weeks, 22.2-29.5 kg) in three groups (G1, G2, G3), and a jejunal single-pass perfusion combined with sampling from the bile duct and the portal, hepatic, and superior caval veins was performed. Fexofenadine was perfused through the jejunal segment alone (G1: 120 mg/l, total dose 24 mg) or with two different verapamil doses (G2: 175 mg/l, total dose 35 mg; and G3: 1000 mg/l, total dose 200 mg). The animals were fully anesthetized and monitored throughout the experiment. Fexofenadine had a low liver extraction (E(H); mean +/- S.E.M.), and the given doses of verapamil did not affect the E(H) (0.13 +/- 0.04, 0.16 +/- 0.03, and 0.12 +/- 0.02 for G1, G2, and G3, respectively) or biliary clearance. The E(H) for verapamil and antipyrine agreed well with human in vivo data. Verapamil did not increase the intestinal absorption of fexofenadine, even though the jejunal permeability of fexofenadine, verapamil, and antipyrine showed a tendency to increase in G2. This combined perfusion and hepatobiliary sampling method showed that verapamil did not affect the transport of fexofenadine in the intestine or liver. In this model the E(H) values for both verapamil and antipyrine were similar to the corresponding values in vivo in humans.