Double left anterior descending artery originating from the left and right coronary artery: A rare coronary artery anomaly

A case of double left anterior descending coronary artery is presented. The double artery originated from the left main stem and the right coronary artery. There were no stenoses on these two arteries. This anomaly of coronary arteries seems to be very rare. © 1993 Wiiey-Liss, Inc.     

Analysis of Intravenous Glucose Tolerance Test Data Using Parametric and Nonparametric Modeling: Application to a Population at Risk for Diabetes

Background:

Modeling studies of the insulin–glucose relationship have mainly utilized parametric models, most notably the minimal model (MM) of glucose disappearance. This article presents results from the comparative analysis of the parametric MM and a nonparametric Laguerre based Volterra Model (LVM) applied to the analysis of insulin modified (IM) intravenous glucose tolerance test (IVGTT) data from a clinical study of gestational diabetes mellitus (GDM).

Methods:

An IM IVGTT study was performed 8 to 10 weeks postpartum in 125 women who were diagnosed with GDM during their pregnancy [population at risk of developing diabetes (PRD)] and in 39 control women with normal pregnancies (control subjects). The measured plasma glucose and insulin from the IM IVGTT in each group were analyzed via a population analysis approach to estimate the insulin sensitivity parameter of the parametric MM. In the nonparametric LVM analysis, the glucose and insulin data were used to calculate the first-order kernel, from which a diagnostic scalar index representing the integrated effect of insulin on glucose was derived.

Results:

Both the parametric MM and nonparametric LVM describe the glucose concentration data in each group with good fidelity, with an improved measured versus predicted r² value for the LVM of 0.99 versus 0.97 for the MM analysis in the PRD. However, application of the respective diagnostic indices of the two methods does result in a different classification of 20% of the individuals in the PRD.

Conclusions:

It was found that the data based nonparametric LVM revealed additional insights about the manner in which infused insulin affects blood glucose concentration.     

Interaction pharmacokinetics of pegylated liposomal doxorubicin (Caelyx) on coadministration with paclitaxel or docetaxel

Purpose To investigate the pharmacokinetics of polyethylene glycol-coated liposomal doxorubicin (PLD, Caelyx) when given as a single agent and in combination with the taxanes paclitaxel or docetaxel in humans.Methods The plasma kinetics of PLD were studied in 19 cancer patients treated with PLD every 4 weeks combined with either paclitaxel (on a weekly basis in seven and as a single infusion in three patients) or docetaxel (weekly in seven and as a single infusion in two). Plasma concentrations of PLD were quantified in two sets of samples per patient to compare the same pharmacokinetic parameters in each subject when treated with single-agent PLD and again with the combination. Total doxorubicin concentrations in plasma were quantified by HPLC. Pharmacokinetics were evaluated by noncompartmental analysis and the data obtained were compared for differences by a matched-pairs nonparametric test.Results Coadministration of paclitaxel produced a median/mean 54/80% increase in PLD AUC_inf (95% confidence interval 23% to 136%, P=0.002). The observed increase was consistent among all subjects. PLD clearance was also decelerated in the presence of paclitaxel (P=0.013) while other pharmacokinetic parameters were affected modestly. A small increase in the AUC of PLD was observed in the docetaxel/PLD arm (mean increase 12%, P=0.039) while PLD clearance decreased marginally and other pharmacokinetic parameters remained unaffected. AUC extrapolated to infinity was below 8% in both arms.Conclusions This study showed the presence of a pharmacokinetic interaction that led to higher plasma concentrations of PLD when combined with paclitaxel and to a minor extent when combined with docetaxel. This pharmacokinetic information may be of value when planning combination therapies of PLD with taxanes.     

Participation of CD45, NKR-P1A and ANK61 antigen in rat hepatic NK cell (pit cell)mediated target cell cytotoxicity

AIM Several triggering receptors have been described to be involved in natural killer (NK) cellmediated target cytotoxicity. In these studies, NK cells derived from blood or spleen were used. Pit cells are liver-specific NK cells that possess a higher level of natural cytotoxicity and a different morphology when compared to blood NK cells. The aim of this study was to characterize the role of the NK-triggering molecules NKR-P1A, ANK61 antigen, and CD45 in pit cell-mediated killing of target cells. METHODS 51 Cr-release and DNA fragmentation were used to quantify target cell lysis and apoptosis, respectively. RESULTS Flow cytometric analysis showed that pit cells expressed CD45, NKR-P1A, and ANK61 antigen. Treatment of pit cells with monoclonal antibody ( mAb ) to CD45 ( ANK74 ) not only inhibited CC531s or YAC-1 target lysis but also apoptosis induced by pit cells. The mAbs to NKRP1A (3.2.3) and ANK61 antigen (ANK61) had no effect on pit cell-mediated CC531s or YAC-1 target cytolysis or apoptosis, while they did increase the Fcγ receptor positive (FcγR+) P815 cytolysis and apoptosis. This enhanced cytotoxicity could he inhibited by 3,4-dichloroisocoumarin, an inhibitor of granzymes. CONCLUSION These results indicate that CD45 participates in pit cell-mediated CC531s and YAC-1 target cytolysis and apoptosis. NKR-P1A and ANK61 antigen on pit cells function as activation structures against FcγR+ P815 cells, which was mediated by the perforin/granzyme pathway.     

Immunoglobulin kappa gene repertoire and somatic hypermutation patterns in follicular lymphoma

Immunoglobulin kappa gene usage and somatic mutation patterns were studied in a series of 47 IGKV-J rearrangements amplified in 42 follicular lymphoma (FL) cases. The IGKV1-39/1D-39 gene predominated and was significantly over-represented compared to normal cells, autoreactive cells or other B cell lymphomas. The impact of somatic hypermutation varied significantly; nevertheless, mutation distribution patterns indicated pressure for preservation of the B cell receptor. In conclusion, the present series demonstrates biased usage of IGKV genes in FL and alludes to the important role of immunoglobulin kappa light chains in antigen selection of the clonogenic B cells in FL.     

The Fate of Transcaval Access Tracts: 12-Month Results of the Prospective NHLBI Transcaval Transcatheter Aortic Valve Replacement Study

Objectives

The authors investigated 1-year outcomes after transcaval access and closure for transcatheter aortic valve replacement (TAVR), using commercially available nitinol cardiac occluders off-label.

Characterization of Brown Adipose Tissue in a Diabetic Mouse Model with Spiral Volumetric Optoacoustic Tomography

Purpose

Diabetes is associated with a deterioration of the microvasculature in brown adipose tissue (BAT) and with a decrease in its metabolic activity. Multispectral optoacoustic tomography has been recently proposed as a new tool capable of differentiating healthy and diabetic BAT by observing hemoglobin gradients and microvasculature density in cross-sectional (2D) views. We report on the use of spiral volumetric optoacoustic tomography (SVOT) for an improved characterization of BAT.

Procedures

A streptozotocin-induced diabetes model and control mice were scanned with SVOT. Volumetric oxygen saturation (sO₂) as well as total blood volume (TBV) in the subcutaneous interscapular BAT (iBAT) was quantified. Segmentation further enabled separating feeding and draining vessels from the BAT anatomical structure.

Results

Scanning revealed a 46 % decrease in TBV and a 25 % decrease in sO₂ in the diabetic iBAT with respect to the healthy control.

Conclusions

These results suggest that SVOT may serve as an effective tool for studying the effects of diabetes on BAT. The volumetric optoacoustic imaging probe used for the SVOT scans can be operated in a handheld mode, thus potentially providing a clinical translation route for BAT-related studies with this imaging technology.

     

High accuracy of mesoscopic epi-fluorescence tomography for non-invasive quantitative volume determination of fluorescent protein-expressing tumours in mice

Objectives

To compare mesoscopic epi-fluorescence tomography (MEFT) and EPRI-illumination reflectance imaging (EPRI) for quantitative tumour size assessment in mice.

Methods

Tumour xenografts of green/red fluorescent protein (GFP/RFP)-expressing colon cancer cells were measured using MEFT, EPRI, ultrasound (US) and micro computed tomography (μCT) at day 14 post-injection (n?=?6). Results from MEFT and EPRI were correlated with each other and with US and μCT (reference methods). Tumour volumes were measured ex vivo by GFP and RFP fluorescence imaging on cryoslices and compared with the in vivo measurements.

Results

High correlation and congruency were observed between MEFT, US and μCT (MEFT/US: GFP: r ²?=?0.96; RFP: r ²?=?0.97, both P?r ²?=?0.93; RFP: r ²?=?0.90; both P?r ²?=?0.96; RFP: r ²?=?0.99; both P?P?r ²?=?0.95; RFP: r ²?=?0.94; both P?r ²?=?0.86; RFP: r ²?=?0.86; both P?Conclusions Fluorescence distribution reconstruction using MEFT affords highly accurate three-dimensional (3D) tumour volume data showing superior accuracy compared to EPRI. Thus, MEFT is a very suitable technique for quantitatively assessing fluorescence distribution in superficial tumours at high spatial resolution.

Key Points

? Mesoscopic epi-fluorescence tomography (MEFT) is an important new molecular imaging technique. ? MEFT allows accurate size determination of superficial tumours with high resolution. ? MEFT is a suitable technique for longitudinal assessment of tumour growth. ? MEFT allows 3D reconstruction and quantification of fluorescence distributions.