A phase II study of sulofenur,a novel sulfonylurea,in recurrent epithelial ovarian cancer

Summary A total of 16 patients with recurrent epithelial ovarian cancer were treated with sulofenur (LY 186641), a novel oral sulfonylurea. All subjects had received previous chemotherapy. Anaemia occurred in all 16 patients, 14 of whom required a blood transfusion, and 2/16 patients received methylene blue for breathlessness due to methaemaglobinaemia. Treatment was discontinued in 2/16 cases due to rising liver enzyme values, which reverted to normal on cessation of the drug. There was no nausea or alopecia. Only two minor responses were seen. Plasma drug levels were insufficient to result in antitumour activity as extrapolated from animal data. Further studies that attempt to increase the bioavailability and improve the therapeutic index are warranted.     

Immunization reverses memory deficits without reducing brain Abeta burden in Alzheimer's disease model

We have previously shown that chronic treatment with the monoclonal antibody m266, which is specific for amyloid beta-peptide (Abeta), increases plasma concentrations of Abeta and reduces Abeta burden in the PDAPP transgenic mouse model of Alzheimer's disease (AD). We now report that administration of m266 to PDAPP mice can rapidly reverse memory deficits in both an object recognition task and a holeboard learning and memory task, but without altering brain Abeta burden. We also found that an Abeta/antibody complex was present in both the plasma and the cerebrospinal fluid of m266-treated mice. Our data indicate that passive immunization with this anti-Abeta monoclonal antibody can very rapidly reverse memory impairment in certain learning and memory tasks in the PDAPP mouse model of AD, owing perhaps to enhanced peripheral clearance and (or) sequestration of a soluble brain Abeta species.     

Photomicrographic images of some features of Uncinaria spp (Nematoda: Ancylostomatidae) from otariid pinnipeds

Photomicrographs of several morphologic features of hookworms (Uncinaria spp) from northern fur seal (Callorhinus ursinus) and California sea lion (Zalophus californianus) pups are presented. The main purpose is to show and describe some physical characteristics of hookworms from the two hosts; it is not to decide from these attributes whether the Uncinaria spp are the same species. The number of species of Uncinaria in pinnipeds is uncertain and specimens need to be examined from the various infected seals and sea lions before the taxonomy of these parasites can be clarified. Information in the present paper should aid in this determination.     

Mechanical properties of dilated human ascending aorta

Dilation of the ascending aorta, associated with Marfan Syndrome, bicuspid aortic valve, or advanced age, may lead to aortic dissection and rupture. Mathematical models can be used to assess the relative importance of increased wall stresses and decreased strength in these mechanical failures. To obtain needed inputs for such models, mechanical properties of dilated human ascending aorta were measured in vitro. Specimens for opening angle, biaxial elastic, and uniaxial circumferential strength tests were cut from excised tissue obtained from 54 patients (age 18–81 years) undergoing elective aortic graft replacement surgery. Opening angle was significantly greater in patients older than 50 years (262°±76°, n=21) compared to younger patients (202°±70°, n=13 All biaxial elastic specimens n=40 exhibited nonlinear stress-strain behavior. Rapid increases in circumferential and axial stresses occurred at lower strains in the older patient group than in the younger. Mean strength was significantly lower in older patients (1.35±0.37 MPa, n=14) than younger (2.04 ± 0.46 MPa, n=11, age <50 years). These changes in mechanical properties suggest that age may influence the risk of aortic dissection or rupture of dilated ascending aorta. © 2002 Biomedical Engineering Society. PAC2002: 8719Rr, 8719Hh     

Optimizing contrast-enhanced abdominal CT in infants and children using bolus tracking

OBJECTIVE: Manual administration of IV contrast material results in unpredictable injection rates. Our purpose was to determine the effect of bolus tracking on overall abdominal helical CT scan quality, particularly on hepatic enhancement, in children with manually administered contrast media. MATERIALS AND METHODS: We compared 33 abdominal helical CT scans of 29 children in whom bolus tracking was used with 22 CT scans of a control group of 21 children in whom bolus tracking was not used. All contrast material was administered by manual injection. Qualitative assessment was made of organ and vessel enhancement and overall scan appearance. Quantitative assessment using region-of-interest cursors was performed at three anatomic levels, and the results for the two groups of children were compared. RESULTS: Qualitative comparison of enhancement parameters between the bolus tracking group (number given first) and the control group (number given second) yielded the following: splenic artifact in 9% versus 23% (p = .24); inferior vena cava flow artifact in 3% versus 27% (p = .01); scanning during the nephrographic phase in 89% versus 59% (p = .02); and good quality grade in 79% versus 64% (p = .23). Significantly greater hepatic enhancement (as measured in mean Hounsfield units) was achieved in the bolus tracking group than in the control group at the superior (48.5 versus 28.6; p < .001), middle (47.9 versus 32.3; p < .001), and inferior (48.2 versus 36.5; p = .01) levels. Hepatic enhancement increased significantly from the superior to the inferior level in the control group (p < .02), whereas enhancement was homogeneous in the bolus tracking group (p > .50). CONCLUSION: Bolus tracking provides improved contrast enhancement, including significantly greater hepatic enhancement, during abdominal helical CT in children in whom the rate of injection of contrast material is unpredictable.     

Dose delivery characteristics of the AIR pulmonary delivery system over a range of inspiratory flow rates.

The purpose of this study was to evaluate the in vitro and in vivo dose delivery characteristics of the AIR pulmonary delivery system over a range of flow rates. A 5-mg placebo powder of engineered particles with low densities (<0.4 g/cc) and large geometric diameters (>5 microm) was delivered via a simple, capsule based, passive dry powder inhaler. The emitted dose, geometric and aerodynamic particle size distributions (aPSDs) were obtained over a range of flow rates (15-60 LPM). The in vitro results demonstrated improved powder dispersion with increasing flow rate through the inhaler. The in vivo dose delivery characteristics were obtained by gamma scintigraphy. Twelve healthy subjects performed the following three inhalation maneuvers: (i) a targeted peak inspiratory flow rate (PIFR) of 20 +/- 10 LPM, (ii) a deep comfortable inhalation, and (iii) a deep forced inhalation. PIFR and inhaled volume were obtained during the inhalation of the dose using a spirometer. In vivo dose delivery was characterized by high and reproducible emitted doses (mean = 87%; inter and intra-subject CV = 5%) and high lung deposition (mean = 51% of the total dose), with low inter and intra-subject CVs (18% and 13%, respectively) across a range of PIFRs (12-86 LPM). Lung deposition of the total dose was shown not to be dependent on PIFR by analysis of variance across the range of inspiratory flow rates (p = 0.29). This was due to the competing effects of smaller aPSDs, increased extrathoracic deposition and higher emitted doses with increasing PIFR. Fully characterizing the effect of inspiratory flow rate requires analysis of the therapeutic response, as well as in vitro dose delivery and lung deposition.     

Added noise affects the neural correlates of upright and inverted faces differently

In five experiments, we examine the neural correlates of the interaction between upright faces, inverted faces, and visual noise. In Experiment 1, we examine a component termed the N170 for upright and inverted faces presented with and without noise. Results show a smaller amplitude for inverted faces than upright faces when presented in noise, whereas the reverse is true without noise. In Experiment 2, we show that the amplitude reversal is robust for full faces but not eyes alone across all noise levels. In Experiment 3, we vary contrast to see if this reversal is a result of degrading a face. We observe no reversal effects. Thus, across conditions, adding noise to full faces is a sufficient condition for the N170 reversal. In Experiment 4, we delay the onsets of the faces presented in noise. We replicate the smaller N170 for inverted faces at no delay but observe partial recovery of the N170 for inverted faces at longer delays in static noise. Experiment 5 demonstrates the interaction in low contrast at a behavioral level. We propose a model in which noise interacts with the processing properties of inverted faces more so than upright faces.     

An involvement of adenosine in cerebral blood flow regulation during hypercapnia

The possibility that endogenously released adenosine, a potent vasodilator, is involved in the increase in cerebral blood flow (CBF) response to hypercapnia has been investigated in an anesthetized, paralyzed rat model. The left retroglenoid vein was cannulated and cerebral venous blood flow measured with a drop counter. Animals were ventilated with a 40% oxygen, 60% nitrogen gas mixture. At 20 min intervals, at a constant rate of flow, the inspired gas mixture was altered to 10% carbon dioxide, 40% oxygen, 50% nitrogen for periods of between 30-90 sec. This brief hypercapnic challenge induced a rapid increase in CBF in the absence of any change in MABP. An involvement of adenosine in this response was demonstrated using an adenosine antagonist, caffeine, an uptake inhibitor, dipyridamole and an adenosine deaminase inhibitor, deoxycoformycin. Caffeine (10 and 20 mg/kg i.p.) 15 min prior to hypercapnic challenges significantly decreased the peak increases in CBF. Dipyridamole (0.1 mg/kg) and deoxycoformycin (0.1 microgram/kg) enhanced the peak increases in flow. These results are consistent with an important role for adenosine in coupling PCO2 to cerebral blood flow.