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Biomedical subjects

G Clarke

Publications and source records attributed to G Clarke.

At least 19 recordsLinked to original sources

High-resolution renal SPECT in eight minutes using a multi-detector gamma camera.

Planar renal scintigraphy with Tc-99m DMSA has become established as a standard diagnostic test to determine if a kidney has been scarred by infection. It has been suggested that high resolution SPECT may improve the sensitivity of detection of renal scars. To determine if it is possible to produce good quality renal SPECT with a short acquisition time, 10 adults were examined with a new multi-detector gamma camera using 8 minute, 16 minute, and 32 minute acquisitions. The number of defects seen (N = 16) with an 8 minute acquisition was not significantly different from the defects (N = 15) seen using a 16 minute and a 32 minute acquisition. In adults when imaging with a multi-detector gamma camera there was no clinical advantage in using an acquisition of longer than 8 minutes.

Adolescent

Bacterial lipopolysaccharide-induced changes in FOS protein expression in the rat brain: correlation with thermoregulatory changes and plasma corticosterone.

In the present study the regions of the brain showing an increase in the number of FOS protein stained cells 180 min following intravenous saline or bacterial lipopolysaccharide (LPS) treatment were investigated and correlated with changes in body temperature and plasma corticosterone levels. Particular attention was given to the possible involvement of the circumventricular organs and regions of the brainstem containing central noradrenergic neurones. LPS at doses of 0.35, 3.5 and 50 micrograms caused highly significant increases in FOS protein expression in the organum vasculosum of lamina terminalis, the area postrema and the subfornical organ compared with saline controls. Marked increases in bacterial lipopolysaccharide-induced FOS protein expression were observed in the ventrolateral medulla, the nucleus of the solitary tract and the locus coeruleus which contain the A1, A2 and A6 noradrenergic neurones respectively. The changes in body temperature induced by LPS were found to be dependent upon the dose of LPS administered; the lowest dose employed (0.35 micrograms) induced an immediate and sustained fever, 3.5 micrograms LPS caused a biphasic response consisting of a hypothermic response followed by a febrile response, whereas 50 micrograms LPS induced a hypothermic response which then normalised by 160 min post-injection. Intravenous saline injection had no significant effect on body temperature. The occurance of LPS-induced hypothermia was coincident with increased FOS expression in the bed nucleus of stria terminalis, which houses vasopressinergic neurones involved in antipyresis, whereas in animals showing an LPS-induced febrile response there was no significant difference in the number of FOS stained cells in the bed nucleus of stria terminalis compared with saline treated animals. LPS also caused marked increases in FOS protein expression in the parvocellular regions of the paraventricular nucleus (pPVN) of the hypothalamus, the central nucleus of the amygdala and the ventral septal area. Plasma corticosterone was unaffected by the lowest dose of LPS (0.35 micrograms), however the higher doses employed (3.5 and 50 micrograms) caused significant increases in plasma corticosterone which correlated with the increases in the number of FOS stained cells in the pPVN. The results of the present study suggest that, in addition to the organum vasculosum of lamina terminalis, the area postrema and subfornical organ may be important in the responses to antigenic challenge that are mediated by the central nervous system. They also add support to the possible involvement of the bed nucleus of stria terminalis in LPS-induced hypothermia and of the involvement of the of the major noradrenergic cell groups (A1, A2 & A6) and a number of hypothalamic and extrahypothalamic forebrain regions in the interaction of immune and central nervous systems.

Animals

Light microscopic and three-dimensional morphology of the human muscular sarcocyst.

Established criteria for morphological typing of sarcocysts was applied to a large series of cases of human skeletal muscle sarcocystosis in Malaysia to determine the type of sarcocyst present. We also wanted to test the general usefulness of this classification and to determine if there are any new cyst types. Three-dimensional (3-D) reconstruction was done to see if the sarcocyst has a distinct 3-D morphology. A total of 66 sarcocysts from 21 cases of human muscle sarcocystosis obtained from a previous prevalence study were examined. Tissue sections (5 microns thick) were stained with haematoxylin and eosin and studied under the light microscope. For 3-D reconstruction, an image analyser was used to align and reconstruct the sarcocyst after microscopic images had been captured with a charge-coupled device (CCD) camera. All the cysts best fit into the type 4 category. This classification is generally useful, although cyst wall characteristics and zoite size appear to be the most reliable criteria for classification. The cyst width averaged 77 microns (range, 30-137.5 microns). Cyst walls were smooth, had no cytophaneres and were less than 1 micron thick. No secondary cyst wall or surrounding inflammation was evident. Numerous cyst merozoites with diameters averaging 1 micron filled the cyst lumen. Although septa were not apparent, in many cysts, zoites were arranged in a unique, curvilinear fashion that suggested their presence. 3-D reconstruction showed the sarcocyst to be a long, tortuous "cylinder" with no branching or other distinguishing feature.

Animals

Inhibition of supraoptic vasopressin neurones following systemic clonidine.

Experiments were undertaken in urethane-anaesthetized rats to investigate the effects of systemic clonidine on the firing of supraoptic vasopressin (VP) neurones, which were identified by their characteristic phasic activity pattern. Injection of clonidine (50 micrograms/kg i.v.) reduced the firing of all 16 VP neurones tested, and their overall mean activity decreased from 5.09 +/- 1.01 to 1.63 +/- 0.64 spikes/second (P < 0.02). In VP cells which were already firing phasically before clonidine, the inhibition resulted in complete quiescence. In VP cells which were originally continuously active, the inhibition resulted in a switch to phasic activity. This inhibitory effect, which was prevented by prior injection of the alpha-2 antagonist idazoxan (0.5 mg/kg), had a mean duration of 11.8 +/- 1.8 min. Subsequent experiments revealed that i.v. clonidine (50 micrograms/kg) caused a transient rise in blood pressure, but this had a shorter time-course and was unlikely to account for the prolonged neuronal inhibition. It was concluded that systemic clonidine acts centrally to suppress the activity of hypothalamic VP neurones, thereby explaining the fall in plasma VP levels found in previous studies.

Animals

The diagnosis and treatment of psoas abscess: a 12 year review.

Over a 12 year period, 25 psoas abscesses occurring in 17 patients were managed at Royal Perth Hospital (900 bed hospital). Symptoms were present, on average, for 5 weeks prior to diagnosis, which was typically confirmed by computerized tomography. Fifty-nine per cent of cases were primary and percutaneous drainage effected a cure in 80% of all cases. Percutaneous drainage resulted in a non-significant trend towards shorter inpatient stay.

Adult

Three forms of stress in Cambodian adolescent refugees.

Sixty-nine Cambodian adolescents and young adults were interviewed to determine their experience as children surviving the Pol Pot regime (1975-1979); their first-year experience of resettlement in this country; and their experience of stressful events during the past year. Current DSM-III-R diagnostic status was also determined. A strong relationship between earlier war trauma, resettlement strain, and symptoms of posttraumatic stress disorder (PTSD) was found. In contrast, the strongest relationship with depressive symptoms was found for recent stressful events. These results are discussed in light of current findings from stress and PTSD research.

Adolescent

A 6-year follow-up study of Cambodian refugee adolescents traumatized as children.

Seventy-three percent of a sample of 46 Cambodian youth interviewed in 1984 and 1987 were reinterviewed in 1990 as part of a pretest for a multisite study of Cambodian refugee trauma now under way. An additional sample of convenience of 38 youth were also interviewed to determine reliability and validity of the diagnostic instruments chosen for the larger study. The DSM-III-R diagnosis of post-traumatic stress disorder (PTSD) was found to persist, but the symptoms appeared less intense over time. In contrast, the prevalence of depression dropped markedly since 1987. Subjects remained largely free of comorbid conditions. Diagnostic reliability and validity were satisfactory. The follow-up sample appeared to be functioning well despite their PTSD profiles. The findings are discussed in light of several current controversies surrounding the concept and measurement of PTSD.

Adolescent

Effects of the kappa-opioid agonist U50,488 on parturition in rats.

1. The effects of the kappa-opioid agonist U50,488 on parturition were studied in the rat. 2. Given directly after the birth of the second pup U50,488 (5 mg or 10 mg kg-1, i.p.) delayed the birth of the subsequent 4 pups by ca. 100 min, acting like morphine (10 mg kg-1, i.p.). In controls given the vehicle i.p., the birth of the 4 pups after treatment took 45.4 +/- 4.6 min. The effects of U50,488 could be prevented by simultaneous naloxone injection (10 mg kg-1). Injection of either U50,488 or morphine at 1 mg kg-1, i.v. also significantly delayed parturition. The effects of U50,488 but not of morphine were fully prevented by preinjection with nor-binaltorphimine (0.5 mg kg-1, i.v.) showing selective kappa-opioid receptor-mediated inhibition by U50,488 of established parturition. 3. In rats with an indwelling jugular venous cannula, i.v. injection of U50,488 (5 mg kg-1) after the birth of the second pup slowed parturition in a similar way to i.p. injection and significantly reduced blood plasma oxytocin concentration measured by radioimmunoassay compared with vehicle-injected controls. 4. Bolus i.v. injections of oxytocin (4 mu once per 5 min) significantly reduced the delay in parturition caused by i.v. U50,488, but continuous i.v. infusion of oxytocin (4 mu 5 min-1) was less effective. 5. Since i.v. oxytocin did not immediately reverse the effects of U50,488 on parturition, direct effects of U50,488 on isometric uterine contractions in vitro were sought. U50,488 inhibited spontaneous or oxytocin-stimulated contractions of uteri from rats within 24 h after parturition in a dose-related manner; the inhibitory effect was not naloxone-reversible.6. Thus U50,488 inhibited established parturition in the rat in a Kappa-opioid selective manner by reducing oxytocin secretion. The inhibitory effect may well have been potentiated by a direct non-opioid depressant action on contractile activity of the uterus.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh

Clinical high resolution skeletal single photon emission tomography using a triple-headed gamma camera.

Planar skeletal scintigraphy has become established as a standard diagnostic test performed within the nuclear medicine department. Since the 1970s good quality images have been produced using an Anger gamma camera and 99Tcm-labelled diphosphonates. Single photon emission tomography (SPET) has improved the sensitivity of detection and the ability to localize bony pathology, particularly benign bone disease in the spine. Recently multi-detector gamma cameras dedicated to SPET have become available. One such system, the Toshiba GCA-9300A, has been used to perform routine clinical skeletal SPET in 81 patients. Good quality images have been obtained using an 8 min acquisition in the axial skeleton and a 16 min acquisition protocol in the peripheral skeleton. Multiple sites can be tomographed in the same patient during the same examination using two or more 8 min acquisitions. Such a multi-detector gamma camera offers advantages over the standard single-headed rotating camera for skeletal SPET in terms of both imaging time and image quality. A cost analysis was performed which demonstrated that the additional cost of purchasing such a multidector gamma camera was less than 30.00 pounds per SPET study.

Bone Neoplasms

The effect of circulating antigen and radiolabel stability on the biodistribution of an indium labelled antibody.

This study has investigated two of the main problems with radiolabelled antibody imaging, the formation of circulating immune complexes (I.C.) and the non specific binding of radiolabel to the antibody molecule. Patients undergoing immunoscintigraphy with 111In labelled monoclonal antibody ICR2 were divided into three groups who received either the radiolabelled antibody alone (control, n = 12), the radiolabelled antibody which was incubated with the chelating agent diethylene triamine pentacetic acid (DTPA) prior to size exclusion chromatography (n = 6) or whose injectate was treated with DTPA and cold MAb administered intravenously prior to radiolabelled MAb administration (n = 6). Radiolabelled antibody uptake in abdominal organs was measured by region of interest analysis using a gamma camera with online computer and that in tumour and normal tissues by gamma well counting of biopsies. Circulating antigen and immune complex was measured by high pressure liquid chromatography (HPLC). The sensitivity of tumour imaging and the tumour uptake of radiolabelled antibody was not significantly different between the groups. Patients with high circulating antigen levels developed high levels of circulating immune complex but also had high tumour uptakes of radiolabelled antibody. Administration of cold MAb increased the splenic, but did not effect the tumour uptake of radiolabelled antibody and only minimally reduced levels of circulating immune complex. Chelate administration reduced the urinary excretion of radioactivity but increased the liver uptake of radioactivity. These results have shown that successful antibody imaging can be carried out despite high levels of circulating antigen, that large doses of unlabelled antibody are required to prevent immune complex formation and that removal of non specifically bound 111In does not reduce the liver uptake of radioactivity.

Aged

Perforation in patients with bleeding ulcer.

Twelve patients developed perforation after haemorrhage in a consecutive series of 840 cases admitted for bleeding chronic peptic ulcer. Death occurred in 3 of the 9 cases with duodenal ulcer and 1 of the 3 cases with gastric ulcer. There were 5 giant and 4 kissing duodenal ulcers and all 3 cases with gastric ulcer had a giant ulcer. The 12 patients were similar to the rest of the series in terms of ulcer site and shock on admission but were older and in poorer medical condition, more had ingested analgesics, more had giant ulcers and the mortality was greater (33% vs 6%). Giant ulceration was the only risk factor of potential clinical value as a predictor of the danger of ulcer perforation. One death occurred in 8 cases treated by early definitive surgery, suggesting this to be the treatment of choice for this unusual complication of peptic ulcer.

Contraindications