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Biomedical subjects

D Carey

Publications and source records attributed to D Carey.

72 records · Page 4Linked to original sources

Identification of the major genetic determinant for neurovirulence of tick-borne orbiviruses.

Three members of the Great Island antigenic subgroup (Kemerovo serogroup) of tick-borne obiviruses produced fatal infections following intracerebral inculation of 2-day-old mice. The average survival times and PFU/LD50 ratios of mice inoculated with Wexford (WEX) virus were significantly greater than those of either Nugget (NUG) or Great Island (GI) virus. Reassortant viruses were isolated following dual infections of cell cultures with a spontaneous temperature-sensitive (ts) mutant of WEX virus, and either NUG wild-type virus or a ts mutant of GI virus. The neurovirulence for mice and derivation of the genomic RNA segments were determined for the reassortants. Analysis of this data revealed that the pathogenic phenotype of the reassortant viruses depended on the parental origin of genomic segment 4. The major genetic determinant of serotype specificity was not shown to influence neurovirulence in these investigations.

Animals↗

Intravenous pentoxifylline in the treatment of rest pain: a preliminary report.

Twenty patients with ischemic rest pain were treated with intravenous pentoxifylline, 1,200 mg daily, for up to three weeks. Ten patients obtained sufficient relief to avoid surgical intervention. Seven of these had complete or near complete relief of rest pain, but the other three required continuing analgesia. Transcutaneous oxygen measurements showed a significant increase after the course of treatment. There were marked gastrointestinal side effects in six patients, necessitating early withdrawal from the study. Three of these six patients had shown a favorable response to medication prior to withdrawal. These preliminary results suggest that pentoxifylline may provide a sufficient increase in tissue oxygen availability to avoid, or at least postpone, surgical intervention. A double blind controlled study is required to further assess the efficacy of this drug as an intravenous treatment.

Aged↗

Antigenic cross-reactions between tick-borne orbiviruses of the Kemerovo serogroup.

Antigenic relationships between the four subgroups of the Kemerovo serogroup of tick-borne orbiviruses were examined. Kemerovo (KEM subgroup), Broadhaven (BRD) and Wexford (WEX) [Great Island (GI) sub-group], Chenuda (CNU sub-group), and Wad Medani (WM sub-group) viruses cross-reacted in immunofluorescence tests. Complement fixation tests (CFT) revealed that KEM virus was more closely related to BRD and WEX viruses than to either CNU or WM viruses. By cross-neutralization, all the viruses were shown to be distinct; only BRD and WEX showed slight cross-reaction. In Vero cells infected with either KEM, BRD, WEX, or CNU viruses, 10 major (p1 to p10) and a variable number of minor virus-induced 35S-labelled polypeptides were detected. Comparison of the polypeptides precipitated by homologous AF revealed close similarities between BRD and WEX viruses but obvious differences between these two viruses and KEM and CNU viruses. In cross-reactions, p6 of KEM and CNU viruses, and p7 of BRD and WEX viruses were immunoprecipitated. Immunofluorescence and immunoprecipitation tests appeared to identify an inter-group specific antigen that was distinct from an intra-group specific antigen detected by CFT. The results support division of KEM-related viruses into 3 new serogroups - KEM (comprising KEM and GI subgroups), CNU and WM - and indicate that a 38 to 43kD polypeptide carries the major inter-group specific antigen.

Animals↗

Characterization of orbiviruses of the Kemerovo serogroup: isolations and serological comparisons.

Nine Orbiviruses of the Kemerovo serogroup were isolated from ticks collected in seabird colonies situated in the U.K., Faeroe Islands, Norway, Morocco and California, U.S.A. Comparison by serological tests with previously reported members of the Kemerovo serogroup demonstrated that viruses isolated from the hard tick, Ixodes uriae, were members of the Great Island subgroup, whereas viruses from soft ticks, Argas monolakensis and Ornithodoros maritimus, belonged to the Chenuda subgroup. Members of the Chenuda group differed from the Great Island group in their ability to produce plaques in Xenopus cell cultures and in the time taken to produce clinical signs in infected mice.

Animals↗

Progesterone synthesis and histology of postpartum bovine corpora lutea.

In vitro progesterone (P(4)) synthesis by corpora lutea (CL) from the first, second or third ovulation after calving was compared and correlated with their histology and cytology. The CL were removed 7 to 12 days after ovulation, and luteal cells isolated by digestion with collagenase. The response of isolated cells to luteinizing hormone (LH) was determined. Hematoxylin-eosin stained tissues were used to study histology, and the distribution of cell types was estimated by stereological methods. Ovulation occurred within 25 days of calving and interovulatory intervals were short, 12.1 +/- 3.9 days and 12.6 +/- 4.8 days, respectively. The CL removed after first ovulation were smaller and contained fewer live cells than those obtained after subsequent ovulations. Stimulation by LH in vitro was independent of cycle number or day of cycle but was related to the histology of the tissue. The CL composed of large cells (> 24 mum) with vacuolated cytoplasm contained high amounts of P(4) but were not stimulated by LH. Conversely, CL composed of small and medium- sized cells (10 to 20 mum) and/or intact larger cells contained little P(4) but were stimulated by LH. These observations indicate that the response of postpartum CL to LH in vitro is dependent upon the structural integrity of the tissue at the time of removal. Furthermore, these observations suggest that the short life of CL during the postpartum period may not be due to the absence of luteotrophic support, but to the action of a luteolytic mechanism.

Journal Article↗

Mixed infections with tick-borne viruses in a seabird colony in Eire.

Viruses were isolated from 2 tick species collected from the nesting areas of seabirds on Great Saltee Island, Eire. Bunyaviruses of the Uukuniemi serogroup were isolated from hard ticks (Ixodes uriae and I. rothschildi), bunyaviruses of the Hughes serogroup from soft ticks (Ornithodoros maritimus), and orbiviruses of the Kemerovo serogroup from I. uriae and O. maritimus. The results indicate that the bunyaviruses, but not the orbiviruses, show "tick specificity". Neutralising activity against members of all 3 serogroups was detected in sera from chicks in the nesting areas; neutralising antibodies were probably maternal.

Animals↗

Comparison of mice and cell cultures for the isolation of tick-borne viruses.

Three methods of isolating viruses from 10 tick pools were compared; none of the methods produced all 13 of the viruses isolated (7 viruses of the bunyaviridae and 6 orbiviruses). Inoculation of homogenised ticks into various cell lines was the most successful, yielding 11 virus isolations. Only 2 tick homogenates induced overt signs of infection following intra-cerebral inoculation of 2-day-old mice. However, when inoculated mouse brain was passaged in various cell lines, 8 of 12 isolations were made. The rates of success of the 3 methods of virus isolation appeared to vary according to the type and titre of the virus in the tick pool.

Animals↗

Orbiviruses and bunyaviruses from a seabird colony in Scotland.

Viruses isolated from ticks (Ixodes uriae) and a kittiwake (Rissa tridactyla) from a seabird colony at St. Abb's Head, Scotland, were shown by complement fixation tests (CFT) to be antigenically related to the Uukuniemi and Kemerovo serogroups. Electron microscopic examination of cell cultures infected with the Kemerovo group viruses revealed particles characteristic of orbiviruses, 72 +/- 3 nm in diam., with an inner core 37 +/- 3 nm in diam., in association with intracytoplasmic, densely staining granular areas, and with fibrillar and tubular structures. Cell cultures infected with the Uukuniemi group viruses revealed characteristic bunyavirus particles, 94 +/- 7 nm in diam., with a closely adherent envelope. Both orbi- and bunyaviruses were isolated from two tick pools and the kittiwake. A third tick pool contained an orbivirus which cross-reacted with the other isolates in CFT and fluorescent antibody tests, but was distinguished from them by neutralization tests.

Animals↗

Capacity and equity in cardiac rehabilitation in the eastern region: good and bad news.

AIM: To document current baseline eligibility for Phase 3 cardiac rehabilitation (CR) and the capacity to meet this need in hospitals in the Eastern Regional Health Authority. METHODS: Information on the eligible population and the capacity for CR was collected in all nine hospitals retrospectively (February-March 2001). RESULTS: Forty-seven per cent of eligible patients were invited to participate with only two-thirds attending. Completion rates were very high (89%) in attenders. Age and health board area were significant independent predictors of being invited to CR. Gender was not independent of age. Fifty-three per cent of the need for this service was met by capacity in the region's nine hospitals in 2000 rising to 59% in 2002. CONCLUSIONS: Many eligible patients are not invited to CR. Lack of capacity is a problem. Among the invited, non-participation is a factor. Inequity in age and inter-hospital variation in invitation is noted.

Adult↗

Trolox and ascorbate: are they synergistic in protecting liver cells in vitro and in vivo?

From in vitro studies involving multilamellar liposomes or other artificial systems, several groups of workers have deduced that Trolox (a water-soluble analogue of vitamin E) and ascorbate are synergistic antioxidants. Here, we demonstrate that while Trolox and ascorbate individually protect cultured hepatocytes against oxyradicals generated either with xanthine oxidase plus hypoxanthine or with hydrogen peroxide, the two antioxidants do not appear to be synergistic when used in equimolar combinations. Also, in a rat model of hepatic ischemia-reperfusion, we observed that infusion of Trolox or ascorbate (7.5-10 mumol/kg body weight) into the postischemic liver reduced the reperfusion injury by 76 or 67%, respectively. However, when both compounds were used together (each at the same dose as used separately), the organ salvage amounted to only 79%. Therefore, there is no evidence of synergism between Trolox and ascorbate in our in vitro and especially in vivo systems.

Animals↗

Albumin-bound bilirubins protect human ventricular myocytes against oxyradical damage.

Synthetic delta-bilirubin (i.e., bilirubin that is covalently bonded to albumin) and, to a lesser extent, bilirubin that is physically adsorbed to albumin substantially prolonged the survival of human ventricular myocytes against in situ generated oxyradicals. This cytoprotection, manifested at micromolar concentrations of either form of bilirubin, surpasses those given by unconjugated bilirubin alone, by equimolar levels of albumin (which has some cytoprotective activity), by known antioxidants ascorbate, mannitol, or Trolox, and by oxyradical scavenging enzymes superoxide dismutase (24,200 IU/L) plus catalase (92,000 IU/L) on the same cells. Our human cell-based data provide the first direct evidence that albumin-bound bilirubins, especially delta bilirubin, are potent circulating cytoprotectors. The latter may be important in defending, among others, the myocardium, which is much less equipped in antioxidant defences than for example the liver or intestines.

Antioxidants↗

Validation of the morphologic end point of necrosis in rat hepatocytes subjected to oxyradical damage.

We have used phase-contrast microscopy to determine a necrotic end point of the order of minutes in primary hepatocytes exposed to oxyradicals generated with xanthine oxidase plus hypoxanthine. This study examines whether the morphologic end point thus determined agrees with other criteria of cell necrosis. When 95-100% of the cells were shown to be necrotic by our morphologic assay, transmission electron microscopy confirmed definitive subcellular evidence of cell death, trypan blue exclusion revealed a 92% loss in the ability of cells to exclude the dye, and there was a 47% specific release of 51Cr (versus a 50% theoretical value). In contrast, the appearance of extracellular aspartate aminotransferase activity was relatively slow and did not corroborate the morphologic end point. In summary, we have validated the morphologic end point in our cell-based assay of oxyradical damage.

Animals↗

Purpurogallin--a natural and effective hepatoprotector in vitro and in vivo.

Purpurogallin is a plant phenol that is sometimes added as an oxidation retardant to fats-oils or to certain fuels or lubricants. However, it was unknown if purpurogallin is cytoprotective. Here we examined this issue, both in isolated hepatocytes and in vivo. From 0.5 to 2.0 mM, purpurogallin prolongs survival of rat hepatocytes substantially against oxyradicals generated with xanthine oxidase and hypoxanthine. The protection was dose dependent and surpassed that given by such antioxidants as ascorbate, mannitol, superoxide dismutase, catalase, and Trolox, when each was examined at or near its optimal concentration in the same system. When 1.5, 3, and 6 mumol of purpurogallin in saline were infused into rats with postischemic livers shortly before reperfusion, the mean hepatic salvages were 42, 76, and 86%, respectively. Such salvage effects would rank purpurogallin highly among the hepatoprotectors known. Over the range of 31 to 500 microM, purpurogallin inhibited the rate of O2 consumption in the xanthine oxidase reaction by approximately 90%, which was 2- to several-fold higher than the inhibition elicited by allopurinol over the same concentrations. Thus, purpurogallin is an effective natural hepatoprotector that may operate partly or principally as an inhibitor of xanthine oxidase.

Allopurinol↗

Acute hemiballismus after carotid endarterectomy--a case report.

A 72-year-old woman who experienced a postoperative stroke after a carotid endarterectomy with the presenting symptom of hemiballismus is described. This unusual presentation was likely the result of a hypotensive episode coupled with a predisposing anatomic variant in the circle of Willis, which compromised blood flow in the posterior cerebral circulation. She responded well to treatment with haloperidol with complete resolution of hemiballistic movements.

Acute Disease↗