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Biomedical subjects

R C Wright

Publications and source records attributed to R C Wright.

At least 19 recordsLinked to original sources

Prevention of isolation-induced hypertension by intrahippocampal administration of a nonpeptide kappa-opioid receptor agonist.

Previous research in this laboratory showed that hypertension in the spontaneous hypertensive rat (SHR) appears to correlate to insufficient production of hippocampal dynorphins, and that blood pressure could be reduced by intrahippocampal administration of dynorphins and nonpeptide kappa agonists. The purpose of the present study was to investigate whether kappa agonists could prevent the development of hypertension in a different hypertensive model, i.e., the isolated male rat model of hypertension (IHR). Isolation of young male rats for 5-7 days in standard rat cages caused an increase in systolic blood pressure from a mean of 132 to 184 mmHg. The blood pressures of rats grouped 3 per cage remained stable. Rats received the nonpeptide kappa agonist U62, 066E, (Spiradoline, Upjohn), 10 nmoles/0.2 microl or drug vehicle bilaterally into the the hippocampus for 3 days prior to and during isolation or grouping. Animals treated with U62, 066E did not develop hypertension as compared to isolated animals treated with vehicle. The isolation procedure used in these studies appears to induce anxietal stress, as indicated by reduced time spent by the rats in the open arms of the elevated-plus maze. This time is increased by U62, 066E, suggesting that the drug possesses anxiolytic properties and may reduce hypertension in part, by blocking an anxiety/stress component. These data strengthen our previous findings that opioids in the hippocampus may be important in restraining increased blood pressure provoked by environmental stimuli such as isolation.

Animals↗

Decreased dynorphin levels and increased kappa opioid receptor binding in male rats with isolation-induced hypertension.

The role of hippocampal dynorphin A (1-8) (Dyn A (1-8)) and kappa opioid receptors was investigated in the isolation-induced hypertensive rat (IHR). Male Sprague Dawley rats were either isolated (1 per cage) or grouped (3 per cage) for 7 days. Isolated rats exhibited increased blood pressure (systolic blood pressure 159.7 +/- 6.6 mmHg) whereas the grouped rats remained normotensive (systolic blood pressure 137 +/- 6.3 mmHg). Using radioligand binding techniques we observed a significant increase in kappa opioid receptor binding in the hippocampus of isolated rats (56% increase) and this further increased when the length of isolation was increased to 2 weeks (72% increase). Radioimmunoassay showed that isolation decreased the hippocampal content of Dyn A (1-8) from 12.7 +/- 0.4 to 11.6 +/- 0.2 pg Dyn A (1-8) per 10 mg tissue (rats weighing approximately 100 g) and from 13.3 +/- 0.8 to 9.7 +/- 1 pg Dyn A (1-8) per 10 mg tissue (approximately 200 g rats). These data suggest that functional alterations in the hippocampal dynorphin system may be involved in the maintenance of isolation induced hypertension.

Animals↗

Hippocampal administration of kappa-opioid receptor antisense exacerbates isolation-induced hypertension.

Isolation of young male Sprague Dawley rats for 7 days provoked hypertension which was exacerbated by hippocampal administration of an antisense oligodeoxynucleotide targeted to the kappa-opioid receptor (1 microg/0.5 microL bilaterally, twice daily, during the isolation or grouping period). Systolic blood pressure rose from a mean of 134 to 162 mmHg in isolated rats treated with antisense and only 139 to 151 mmHg in grouped rats treated with antisense. In grouped rats treated with either vehicle or missense, isolation caused a mean increase in systolic blood pressure of only 16 and 14 mmHg respectively. Neither the missense oligodeoxynucleotide nor the vehicle had any significant effects upon systolic pressure in grouped rats, which had not been isolated. Pharmacological studies indicated that rats previously treated with the antisense had no significant depressor response to U62, 066E (a non-peptide kappa agonist known to reduce blood pressure acutely when administered into the hippocampus), however rats previously treated with vehicle or missense exhibited a significant hypotensive response to the drug. This implies that the antisense had reduced the density or activity of the kappa receptors within the hippocampal formation. These data are in accordance with our previous studies, i.e. in several rat models of hypertension, the increase in blood pressure may be modulated via hippocampal kappa opioid receptors.

Animals↗

Kappa-opioid receptor antisense oligonucleotide injected into rat hippocampus causes hypertension.

Bi-hippocampal microinjection treatment (1 microg per side, twice a day for 5 days) with an antisense phosphorothioate oligodeoxynucleotide antisense oligodeoxynucleotide to the rat kappa-opioid receptor, caused hypertension in normotensive Wistar Kyoto (WKY) rats and increased the blood pressure of spontaneously hypertensive rats (SHR). Systolic blood pressure in WKY rats increased from 121+/-4 to 153+/-6 mm Hg, and in SHR systolic blood pressure increased from 153+/-4 to 183+/-5 mm Hg. Similar results were observed with mean blood pressure, however, there were no changes in heart rate. No significant responses were seen with either vehicle or missense injections. Radioligand binding studies indicated that there was a significant decrease in apparent kappa-opioid receptor density due to antisense oligodeoxynucleotide treatment. The results are in accord with our earlier suggestions that the kappa-opioid system in the hippocampus may have a role in the neural control of blood pressure.

Animals↗

Real-time interactive color flow MR imaging.

Real-time interactive color flow magnetic resonance (MR) imaging is a combination of real-time MR imaging and color encoding of velocity-induced phase angle. Flow-compensated (FC) and flow-encoded (FE) images are acquired continuously by using gradient echoes and a 12-msec repetition time. Each image is reconstructed within 200 msec of acquisition, and the FC magnitude image is displayed in gray-scale format. The phase difference between the reconstructed FC and FE images, a difference proportional to velocity along the flow-encoding direction, is encoded in color and superimposed on the gray-scale FC image. Magnitude and phase information are thus presented simultaneously. The viewer may interactively adjust many acquisition parameters during data acquisition. Experimental results of phantom and in vivo human studies validate the method. Characteristics of the color flow MR imaging technique are compared with those of duplex color ultrasound.

Blood Flow Velocity↗

Treatment cost and rehospitalization rate in schizophrenic outpatients with a history of substance abuse.

Retrospective self-report data from 60 chronic schizophrenic outpatients in a community support program (CSP) were used to study the relationship between a history of substance abuse and rate of psychiatric rehospitalization and outpatient treatment cost. The sample showed a significant overall reduction in days spent in a psychiatric hospital or jail and in outpatient treatment expenses during the first year in the CSP. Although subjects with recent symptoms of substance abuse (N = 27) showed consistently smaller reductions than subjects with no history of substance abuse (N = 17) or subjects with no recent substance abuse symptoms (N = 16), the only significant difference between the groups was in the total number of days spent in an institution. However, the findings suggest that treatment of patients with concurrent substance abuse and schizophrenia is disproportionately more costly than that of patients without dual diagnoses.

Adult↗

Real-time interactive magnetic resonance imaging.

We describe a system for performing interactive MRI in real time. Using a TR/TE 7.1/3.5 ms sequence, the operator may alter a scan parameter and observe the effects of the alteration on the image within a few hundred milliseconds. With this system, we can interactively control the oblique scan slice orientation and, using inversion pulses, the image contrast.

Fluoroscopy↗

High-speed line scan MR angiography.

We describe a system which forms MR angiographic images at high speed. Multiple axial sections are imaged sequentially using a 2DFT GRASS sequence with TR/TE 50/15 ms, 64 phase encodings per image. Reconstruction and projection of each image are performed immediately (within 220 ms) after data for that image are acquired. The projection angiogram is constructed line by line as the scan progresses, thereby totally eliminating any additional time required for reconstruction and projection.

Blood Vessels↗

New porous organic microspheres for high-performance liquid chromatography.

A process for producing spherical porous organic microspheres, based on urea-formaldehyde (UF) polymer, has been developed. These microspheres exhibit exceptional mechanical strength and resiliency and have minimal tendency toward shrinking or swelling in aqueous, organic, or hydroorganic media. The geometric parameters of the microspheres are conveniently adjusted by process variables, which allow precise control of pore and particle dimensions. The surface of the UF microsphere contains organic functional groups suitable for chemical modification so that ligands of choice may be covalently attached for operation in the anion-exchange or hydrophobic interaction modes.

Chromatography, High Pressure Liquid↗

Compensation for effects of linear motion in MR imaging.

Various compensation methods for different types of motion during MR image acquisition have been proposed. Presented here is a postprocessing scheme for eliminating artifacts due to linear, intra-slice motion of known velocity. The data for each phase encoding or "view" acquired from a moving object are shown to differ from those which would be measured from the stationary object by a phase factor which depends on the object's displacement from a reference point. This derivation is then used to propose a correction scheme for linear motion in which all phase encodings measured at different positions of the moving object are collapsed onto the same reference position. After subsequent reconstruction, the object appears perfectly "focused." By selection of different reference positions, the method permits positioning of the compensated object as desired within the field of view of the image. This property allows the method to be extended to create sequences of corrected images with smooth object motion between frames of the sequence. The basic correction scheme and its variations were tested experimentally in phantom studies with velocities as large as 8 cm/s.

Humans↗

Real-time MR fluoroscopic data acquisition and image reconstruction.

We describe an experimental system for performing high-speed reconstruction of MR image data acquired with a GRASS sequence. System characteristics are an image acquisition time of 627 ms, continuous image reconstruction at a rate of 6 images/s, and an image reconstruction time of 120 ms. The results is a system for performing MR imaging in real time.

Equipment Design↗

The survival patterns of selected faecal bacteria in tropical fresh waters.

The survival of various faecal bacteria used as indicators of the faecal contamination of water supplies has been investigated in a tropical environment (Sierra Leone). Isolates representing the thermotolerant coliform (TtC) and faecal streptococcus (FS) groups, Clostridium perfringens and Salmonella spp. were studied over a 48 h period of immersion in water from three different sources. Survival patterns varied according to source type, but some general observations were made: a portion of the TtC group was apparently capable of substantial regrowth; FS organisms died off at a faster rate than TtC organisms initially, but survived longer; vegetative cells of C. perfringens died off rapidly; and Salmonella spp. could survive for as long as the other faecal organisms tested. The implications of results for the analysis of tropical waters for faecal contamination are discussed.

Bacteria↗

MR fluoroscopy: initial clinical studies.

Magnetic resonance (MR) fluoroscopy is a method for high-speed MR image acquisition with the goals of short acquisition time per image (500 msec or less), high image rate (10 images or more per second), and high-speed image reconstruction (150 msec or less from data acquisition to image display). The authors present their results with the first two goals in volunteers. MR fluoroscopic image data were acquired with a limited flip angle pulse sequence with reduced repetition times (TRs) and fewer phase encodings used per image. The sequence was applied continuously, and images were formed by updating one set of data with data from the most recently taken measurements. Sample head images were generated with TR/echo times as small as 11/5.5 msec and 48 phase encodings for a total acquisition time of about 500 msec. Images were acquired while the volunteer flexed his head. Artifacts from the motion became less evident on images as progressively shorter acquisition times were used.

Brain↗

MR fluoroscopy: technical feasibility.

A method of magnetic resonance image acquisition and reconstruction is described in which high imaging rates and fast reconstruction times are allowed. The acquisition is a modification of the basic FLASH sequence but with a restricted number N of phase encodings. The encodings are applied sequentially, periodically, and continuously. Images are formed by sliding a window of width N encodings along the acquired data and reconstructing an image for each position of the window. In general the acquisition time per image exceeds the time between successive images, and the method thus has a temporal lag. Experimental studies were performed with a dynamic phantom using 48 phase encodings and a TR of 20 ms, for an image acquisition time of about 1 s. The image display rate in the reconstructed sequence was 12.5 images/s, and the image sequence portrayed the motion of the phantom. Additional studies were done with 24 encodings. It is shown how the sliding window technique lends itself to high-speed reconstruction, with each newly acquired echo used to quickly update the image on display. The combination of the acquisition technique described and a hardware implementation of the reconstruction algorithm can result in realtime MR image acquisition and reconstruction.

Fluoroscopy↗

The seasonality of bacterial quality of water in a tropical developing country (Sierra Leone).

Natural water sources used as drinking-water supplies by rural settlements in Sierra Leone were examined monthly over a one-year period to detect any seasonal variations in bacterial quality. The 37 degrees C colony count, levels of selected faecal indicator bacteria and the incidence of Salmonella spp. were monitored. A seasonality was demonstrated for all the variables, counts generally increasing with the progression of the dry season, culminating in peaks at the transition from dry to wet season. Some complications with respect to the interpretation of counts of faecal indicator bacteria from raw tropical waters are noted.

Clostridium perfringens↗

Magnetic resonance image synthesis. Clinical implementation.

Magnetic resonance (MR) image synthesis is a technique enabling the retrospective optimization of scanning parameters. This paper describes the methods used to enable the clinical implementation of this technique. It is shown that effective synthetic images can be generated from only three acquired images per slice. Data for 16 slices and TR times of 500 and 2000 ms can be efficiently acquired in a multi-slice multi-echo dual-TR pulse sequence. Computation of T1, T2, and density images and the subsequent synthesis of images for arbitrary TR and TE times can be performed at high speed with dedicated hardware. The method is seen as one of standardizing acquisition protocols and thereby improving patient throughput. Specific clinical applications are discussed.

Humans↗