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Biomedical subjects

J T Richards

Publications and source records attributed to J T Richards.

At least 19 recordsLinked to original sources

Optic flow dominates visual scene polarity in causing adaptive modification of locomotor trajectory.

Locomotion and posture are influenced and controlled by vestibular, visual and somatosensory information. Optic flow and scene polarity are two characteristics of a visual scene that have been identified as being critical in how they affect perceived body orientation and self motion. The goal of this study was to determine the role of optic flow and visual scene polarity on adaptive modification in locomotor trajectory. An object is said to have visual polarity, or to be "visually polarized", when it contains an identifiable principal axis with one end distinct from the other. Two computer-generated virtual reality scenes were shown to subjects during 20 min of treadmill walking. One scene was a highly polarized scene, while the other was composed of objects displayed in a non-polarized fashion. Both virtual scenes depicted constant rate self motion equivalent to walking counterclockwise around the perimeter of a room. Subjects performed Stepping Tests blindfolded before and after scene exposure to assess adaptive changes in locomotor trajectory. Subjects showed a significant difference in heading direction, between pre- and post-adaptation Stepping Tests, when exposed to either scene during treadmill walking. However, there was no significant difference in the subjects' heading direction between the two visual scene polarity conditions. Therefore, it was inferred from these data that optic flow has a greater role than visual polarity in influencing adaptive locomotor function.

Adaptation, Psychological↗

Exposure to a rotating virtual environment during treadmill locomotion causes adaptation in heading direction.

The objective of this study was to investigate the adaptive effects of variation in the direction of optic flow, experienced during linear treadmill walking, on modifying locomotor trajectory. Subjects (n=30) walked on a motorized linear treadmill at 4.0 km h(-1) for 24 min while viewing the interior of a 3D virtual scene projected on to a screen 1.5 m in front of them. The virtual scene depicted constant self-motion equivalent to either (1) walking around the perimeter of a room to one's left (Rotating Room group) or (2) walking down the center of a hallway (Infinite Corridor group). The scene was static for the first 4 min and then constant rate self-motion was simulated for the remaining 20 min. Before and after the treadmill locomotion adaptation period subjects performed five stepping trials. In each trial they marched in place to the beat of a metronome at 90 steps min(-1) for a total of 100 steps while blindfolded in a quiet room. The subject's final heading direction (deg) and final X (fore-aft, cm) and final Y (medio-lateral, cm) positions were measured for each trial. During the treadmill locomotion adaptation period subjects' 3D torso position was measured. We found that subjects in the Rotating Room group, as compared with the Infinite Hallway group: (1) showed significantly greater deviation during post-exposure testing in the heading direction and Y position opposite to the direction of optic flow experienced during treadmill walking; and (2) showed a significant monotonically increasing torso yaw angular rotation bias in the direction of optic flow during the treadmill adaptation exposure period. Subjects in both groups showed greater forward translation (in the +X direction) during the post-treadmill stepping task that differed significantly from their pre-exposure performance. Subjects in both groups reported no perceptual deviation in position during the stepping tasks. We infer that viewing simulated rotary self-motion during treadmill locomotion causes adaptive modification of sensorimotor integration in the control of position and trajectory during locomotion, which functionally reflects adaptive changes in the integration of visual, vestibular, and proprioceptive cues. Such an adaptation in the control of position and heading direction during locomotion, because of the congruence of sensory information, demonstrates the potential for adaptive transfer between sensorimotor systems and suggests a common neural site for processing and self-motion perception and concurrent adaptation in motor output.

Adaptation, Physiological↗

Epidural anaesthesia as a method of pre-emptive analgesia for abdominal hysterectomy.

The effect of pre- versus postincisional epidural blockade without the use of systemic opioids was investigated in a randomised, double-blind study of two groups of 25 patients undergoing abdominal hysterectomy performed under general anaesthesia. The first group received, via a lumbar epidural catheter, 0.9% saline (16 ml) 15 min prior to surgical incision and 0.5% bupivacaine (15 ml) and fentanyl 50 micrograms (1 ml) 15 min prior to skin closure. The second group of 25 patients received the same amount of bupivacaine and fentanyl 15 min pre-incision and saline prior to skin closure. Visual analogue pain scores and patient-controlled morphine consumption were measured at specified times for 48 h. We were unable to detect any significant difference in either of the outcome measures of the two groups and thus were unable to demonstrate that epidural blockade using local anaesthetic and opioid has a pre-emptive effect.

Adult↗

An evaluation of the Bio-Rad Variant Haemoglobin Testing System for the detection of haemoglobinopathies.

The Bio-Rad Variant Haemoglobin Testing System is an automated analyser which uses the principle of cation exchange high performance liquid chromatography. This evaluation was undertaken to examine the effectiveness of the instrument as a screening mechanism to assist in the diagnosis of haemoglobinopathies. The ability to quantify haemoglobins A2 and F and to 'flag' other haemoglobin variants was tested. Within-batch precision was excellent and between-batch precision was good. Linearity and sensitivity compared favourably with the manufacturer's published ranges. The level of carry-over for haemoglobins F, S and A was less than 0.25%. The mean carry-over for haemoglobin A2 was 2.08%. This higher figure reflected the smaller absolute difference between the high and low samples for this parameter. The instrument never failed to indicate the presence of an abnormal haemoglobin in 271 selected samples. The instrument was reliable throughout the evaluation and at no time was a run aborted.

Cations↗

Ethnicity study and non-selective screening for haemoglobinopathies in the antenatal population of central Manchester.

The objective of this study was to determine the frequency of ethnic groups within the antenatal population in central Manchester and thereby ensure that the haemoglobinopathy service was targeting the correct population and their needs. Ethnic data collection records of 6718 patients were analysed over a 7 month period. Of these 62.3% stated that they were White, 13.2% Asian, 7.9% Black, 3.8% Chinese or 'other ethnic groups' and 12.7% gave no information about their ethnic background. A subset of 1144 patients were screened for haemoglobinopathies over a 1 month period. The incidence of haemoglobinopathies within the screened population was 2.62%, and comprised 0.69% beta thalassaemia trait, 1.22% sickle cell trait, 0.43% haemoglobin C trait and 0.26% haemoglobin D trait. The total incidence of haemoglobinopathies was highest within the Black population (18.2%), followed by the no information group (5.6%), Asian (3.35%) and white (0.26%). The high proportion of ethnic minorities and the significant carrier frequency in the no information group, support our view that non-selective screening should be offered to the antenatal population of central Manchester.

England↗

Comet assay studies on the activation of two diaziridinylbenzoquinones in K562 cells.

Two versions of the comet assay have been used to identify the difference in the modes of action of AZQ (2,5-diaziridinyl-3,6-bis(carboethoxyamino)-1,4-benzoquinone) and BZQ (2,5-diaziridinyl-3,6-bis(ethanolamino)-1,4-benzoquinone) in human leukaemia K562 cells and a K562-derived resistant cell line, BZQR. Using the standard alkaline assay, AZQ produced dose-dependent changes in the mean comet moments from K562 cells, consistent with the formation of strand breaks. This damage was repaired over a period of 6 hr after removal of the drug. The resistant cell line, BZQR, showed much smaller changes in comet moment under identical conditions. In contrast to AZQ, BZQ did not produce any measurable strand breaks in the K562 or BZQR cells. However, the comet radiation/crosslinking assay and a fluorescence-based assay revealed that BZQ extensively cross-links DNA in K562 cells. The extent of cross-linking is greatly reduced in the resistant cell line.

Antineoplastic Agents↗

Urinary hydroxyproline and serum alkaline phosphatase in sickle cell disease.

Serum alkaline phosphatase, alkaline phosphatase isoenzymes, and urinary hydroxyproline excretion were studied in 20 young adult sickle cell patients and 58 matching normal controls. Total alkaline phosphatase was significantly higher in the sickle cell patients than in controls. Heat inactivation test and isoenzyme electrophoresis indicated that bone is the predominant isoenzyme in patients. Hydroxyproline excretion was significantly higher in the sickle cell patients than in controls. Serum total alkaline phosphatase correlated well with urinary hydroxyproline excretion in sickle cell patients (r = 0.73). Both alkaline phosphatase and hydroxyproline increased with age in the sickle cell patients. This study suggests that delayed growth and/or bone destruction may contribute to the elevated levels of alkaline phosphatase and urinary hydroxyproline.

Adolescent↗

Simple method for granulocyte-macrophage cell culture and staining in soft agar: comparison with a standard research technique.

A modified, small volume, two phase, disc culture system for CFU-GM (seven and 14 days of incubation) was compared with a standard single layer system. The 1 ml single layer cultures were counted unstained in situ before both sets of cultures were transferred to glass slides for staining. Bone marrows were cultured from forty eight subjects, including normal controls and patients with acute non-lymphoblastic leukaemia, acute lymphoblastic leukaemia, and myelodysplastic syndrome. Observer error was least with the disc cultures, whereas variation between replicate cultures was similar for both methods. A high degree of correlation was found between the two methods for both day 7 (r = 0.90) and day 14 (r = 0.91) cultures. The number of colonies and clusters was higher with the disc system, indicating better cloning efficiency. Analysis of subsets of clinical groups showed similar patterns of abnormality with both systems. The simplicity of the method makes the use of this technology possible in most laboratories, and the superior morphological resolution may increase the clinical usefulness of such studies.

Bone Marrow↗

Acyclovir treatment of disseminated herpes simplex virus type 2 infection in weanling mice: alteration of mortality and pathogenesis.

Intranasal inoculation of weanling mice with herpes simplex virus type 2 (HSV-2) provides an experimental infection that closely resembles disseminated and central nervous system HSV infections of human neonates. Intraperitoneal treatment with acyclovir (ACV) successfully reduced mortality even when therapy was begun as late as 2 days and oral therapy as late as 4 days after viral challenge. Treatment with ACV beginning on day 1 completely inhibited HSV-2 replication in lung, spleen, kidney, olfactory lobe, and cerebrum and decreased viral titers in the pons by 2-3 logs. Comparison of these data with our previous experiments using adenine arabinoside and adenine arabinoside 5' monophosphate indicates that ACV is more effective in the murine model of neonatal disease and suggests that ACV may also be more effective in treating the disease in humans.

Acyclovir↗

Topical butylated hydroxytoluene treatment of genital herpes simplex virus infections of guinea pigs.

The effect of topical treatment with butylated hydroxytoluene (BHT) was evaluated in primary and recurrent genital herpes simplex virus type 2 (HSV-2) infection of guinea pigs. In the first experiment, treatment with placebo, 5%, 10%, or 15% BHT was initiated 48 h after viral inoculation and continued 4 times daily for 15 days. During primary infection no differences in maximum lesion severity or titers of virus in lesions were observed, however, lesion duration was reduced in BHT-treated animals resulting in a significantly smaller lesion score-day area under the curve. In a second experiment using U.S.P. mineral oil as an additional placebo, BHT placebo and 15% BHT in a double blind trial, similar results were obtained. Treatment of the recurrent infection in either experiment failed to alter the number of recurrent episodes or days with lesions.

Administration, Topical↗

Recurrent genital herpes simplex virus infection in guinea pigs.

After recovery from initial genital herpes simplex virus (HSV) infections, female guinea pigs developed spontaneous recurrent infections characterized by discrete erythematous or vesicular herpetic lesions on the external genital skin. HSV type 2 (HSV2) caused significantly more recurrent infections in guinea pigs than did HSV type 1 (HSV1). HSV2-infected animals demonstrated a significant decline in frequency of recurrences over time. The viral nature of the recurrent lesions was confirmed by recovery of infectious HSV, detection of HSV antigen, and histologic examination. Latent HSV2 could be demonstrated in dorsal root ganglia and external genital skin after recovery from the primary infection. Recurrent genital HSV infection in the guinea pig shares many features with recurrent genital herpes in humans and provides a model for studying the relationship between latency and recurrences and for exploring methods for control of recurrent disease.

Animals↗

Acyclovir treatment of experimental genital herpes simplex virus infections. I. Topical therapy of type 2 and type 1 infections of mice.

Intravaginal inoculation of mice with herpes simplex virus (HSV) provides a model infection of genital herpes to determine the effectiveness of potential antiviral agents. topical (intravaginal) treatment with 1% or 5% acyclovir (ACV) in an ointment of gel vehicle initiated 3, 6 or 24 h after inoculation with HSV type 2, significantly inhibited viral replication in the genital tract and usually reduced final mortality. Treatment with 5% ACV initiated 48 or 72 h after infection also reduced vaginal virus titers but did not alter final mortality. When mice were inoculated with HSV type 1 treatment with 5% ACV significantly reduced viral replication in the genital tract when begun as late as 72 h. In HSV-2 infected mice, treatment initiated 3 h but not 24 h after infection prevented the establishment of latent infection in sacral ganglie. These results suggest that topical ACV may be effective antiviral agent for primary genital herpes in humans.

Acyclovir↗

Recombination kinetics following nanosecond laser photolysis of carbonmonoxyhaemogloblin.

The kinetics of the ultrafast ligand recombination following 347 nm laser photolysis of aqueous solutions of carbonmonoxyhaemogloblin have been investigated. The process is biphasic and the rate constants for the two processes as functions of temperature have been used to give activation energies of 6 +/- 3.9 kJ . mol-1 for the fast process and 31 +/- 4.8 kJ . mol-1 for the slow process. Frequency factors have also been calculated. The two processes are discussed in relation to both low-temperature studies and model calculations on the rate of entry of carbon monoxide into haem proteins.

Carbon Dioxide↗

Optimal treatment of herpes simplex virus encephalitis in mice with oral acyclovir.

The effect of oral or intraperitoneal administration of acyclovir was evaluated in four experimental models of herpes simplex virus (HSV) encephalitis in mice. Mice were inoculated with HSV-1 or HSV-2 intracerebrally or with HSV-2 intranasally, intraperitoneally, or intravaginally. With all four routes of inoculation, oral acyclovir therapy significantly reduced mortality when started as late as 72 to 96 hours after viral challenge. Intraperitoneal acyclovir was not effective in protecting mice inoculated intravaginally, but was effective if given 24 to 48 hours after intracerebral or intranasal challenge and as late as 96 hours after intraperitoneal infection. Oral acyclovir was more active than intraperitoneal treatment in all four model infections. Levels of acyclovir inhibitory for HSV in cell culture were maintained in plasma and brain tissue throughout oral treatment but lasted only three to six hours after each intraperitoneal treatment. These results suggest that acyclovir may be useful in treating serious HSV infections in humans.

Acyclovir↗

Effect of acyclovir treatment on acute and chronic murine cytomegalovirus infection.

Murine cytomegalovirus (MCMV) is inhibited in vitro by 1 to 2 microM acyclovir. Therapy of a systemic MCMV infection in weanling mice with acyclovir was only minimally effective when drug was administered intraperitoneally, while oral administration by addition of acyclovir to the drinking water was highly efficacious in mice with disseminated MCMV. Effective therapy was characterized by reduction of virus titers in lung, liver, spleen, and kidney. In mice chronically infected with MCMV, treatment for 30 days with oral acyclovir eliminated or reduced virus titers in all target organs except the salivary gland. Therapeutic efficacy in this model infection using oral administration of acyclovir could be correlated with the achievement of acyclovir levels in the plasma of experimental animals two to 10 times greater than the mean inhibitory concentration for MCMV in vitro throughout treatment. The lack of efficacy observed when drug was administered intraperitoneally was associated with acyclovir levels exceeding 1 microM for one to three hours after each dose.

Acute Disease↗

Anti-herpesvirus activity of adenine arabinoside analogues in tissue culture and a genital infection of mice and guinea pigs.

Four analogues of adenine arabinoside (ara-A) were compared for activity against herpes simplex virus (HSV) in tissue culture and in a genital infection of mice and guinea pigs. These analogues, 5'-monophosphate (ara-AMP), 5'-valerate ester (ara-AV), 2'3'-diacetate ester (ara-ADA), and 2',3',5'- triacetate ester (ara-ATA) have greater water and lipid solubility and resistance to deamination than ara-A. In mouse embryo fibroblast cells, similar viral inhibitory levels were noted with ara-A, AMP, and ara-Av, while ara-ADA and ara-ATA were 6-10 time less active. In mice infected intravaginally with HSV type 2 (HSV-2), intravaginal treatment with 10% concentrations of each of the compounds beginning 3 h after viral challenge, had no effect on infection rates, titers of virus in vaginal secretions, mortality rates or the mean day of death as compared with placebo-treated controls. In the HSV-2 genital infection of guinea pigs, treatment with 10% vaginal creams or placebo vehicle was initiated 6 or 24 h after viral inoculation. In animals treated at 6 h with ara-A, ara-AMP and ara-AV, there was complete inhibition of viral replication in the vaginal tract and development of external genital lesions. When treatment with these three drugs was delayed 24 h after infection, there was no effect on vaginal virus titers, but lesions severity was reduced by ara-A or ara-AMP therapy. Ara-ATA was ineffective whether begun at 6 or 24 h. The greater solubility in water and lipid as well as the resistance to deamination of ara-AMP and ara-AV did not appear to enhance their antiviral activity over that of ara-A. Additionally, ara-ADA and ara-ATA exhibited less activity both in tissue culture and in the experimental genital infections.

Administration, Topical↗