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W Yu

Publications and source records attributed to W Yu.

At least 217 records · Page 12Linked to original sources
PubMed1997

Identification of a microtubule-associated motor protein essential for dendritic differentiation.

The quintessential feature of the dendritic microtubule array is its nonuniform pattern of polarity orientation. During the development of the dendrite, a population of plus end-distal microtubules first appears, and these microtubules are subsequently joined by a population of oppositely oriented microtubules. Studies from our laboratory indicate that the latter microtubules are intercalated within the microtubule array by their specific transport from the cell body of the neuron during a critical stage in development (Sharp, D.J., W. Yu, and P.W. Baas. 1995. J. Cell Biol. 130:93- 104). In addition, we have established that the mitotic motor protein termed CHO1/MKLP1 has the appropriate properties to transport microtubules in this manner (Sharp, D.J., R. Kuriyama, and P.W. Baas. 1996. J. Neurosci. 16:4370-4375). In the present study we have sought to determine whether CHO1/MKLP1 continues to be expressed in terminally postmitotic neurons and whether it is required for the establishment of the dendritic microtubule array. In situ hybridization analyses reveal that CHO1/MKLP1 is expressed in postmitotic cultured rat sympathetic and hippocampal neurons. Immunofluorescence analyses indicate that the motor is absent from axons but is enriched in developing dendrites, where it appears as discrete patches associated with the microtubule array. Treatment of the neurons with antisense oligonucleotides to CHO1/MKLP1 suppresses dendritic differentiation, presumably by inhibiting the establishment of their nonuniform microtubule polarity pattern. We conclude that CHO1/MKLP1 transports microtubules from the cell body into the developing dendrite with their minus ends leading, thereby establishing the nonuniform microtubule polarity pattern of the dendrite.

Animals↗
PubMed1997

c-Jun involvement in vitamin E succinate induced apoptosis of reticuloendotheliosis virus transformed avian lymphoid cells.

Previous studies have shown that treatment of avian reticuloendotheliosis virus-transformed RECC-UTC4-1 (C4-1) lymphoblastoid cells with 10 microg/ml (18.8 microM) of RRR-alpha-tocopheryl succinate (vitamin E succinate, VES) for 3 days induced approximately 50% of the cells to undergo apoptosis. Elevated and prolonged expression of c-jun mRNA and protein was temporally correlated with VES-induced cell death. Data presented in this paper show that the elevated and prolonged expression of c-jun message and protein are not accounted for by enhanced stability, and show the involvement of c-Jun in VES-induced apoptosis in this lymphoblastoid cell type. C4-1 cells infected with a virus carrying a dominant, negatively acting mutant form of c-Jun, supjun-1, exhibited: (i) 71% reduction in VES-induced apoptosis, (ii) a 2.0-2.5-fold decrease in wildtype, endogenous c-Jun expression, and (iii) a 2.4-2.6-fold reduction in AP-1 binding activity. Additionally, cells co-treated with VES plus RRR-alpha-tocopherol, exhibited a 70% reduction in apoptosis, a marked reduction in c-Jun expression and a 1.6-fold reduction in AP-1 binding activity. These studies suggest that c-Jun plays a crucial role in VES-induced apoptosis in C4-1 cells, and add to our understanding of mechanisms of action involved in VES-mediated tumor cell growth inhibition.

Animals↗
PubMed1997

Quantitative comparison of global carbohydrate structures of glycoproteins using LC-MS and in-source fragmentation.

A comparative method for the quantitative analysis of the ratio of oxonium fragment (reporter) ions derived from sialic acid and N-acetylhexosamine residues on a large intact glycoprotein, the B domain of recombinant human factor VIII (rhFVIII), was developed. The method utilized liquid chromatography-electrospray ionization mass spectrometry (LC-ESI MS) on a single-quadrupole instrument. During development, systematic approaches such as full-matrix and simplex strategies were used for the optimization of the signal-to-noise ratio by controlling source temperature and cone voltage. The method was found to be precise (RSD = 0.84%), sensitive (capable of differentiating 1 sialic acid residue change among at least 29 sialic acids on a 103-kDa glycoprotein that is 38% carbohydrate), applicable to a wide range of loading (11.6-372 micrograms of FVIII), and accurate according to a comparison to matrix-assisted laser desorption-ionization time-of-flight mass spectrometry. Combining the method with enzymatic removal of N-glycans, selective O-glycan analysis was also performed leading to differential fragment ion analysis ascribed to N- and O-glycans. Quantitative ESI in-source dissociation MS combined with LC can generally be used for glycoproteins, as one of the indicators, to compare the distribution of carbohydrate residues over N- and O-glycans, to investigate their isoforms, and compare batch-to-batch characteristics of biopharmaceuticals.

Amidohydrolases↗
PubMed1997

A specific host cellular protein binding element near the 3' end of mouse hepatitis virus genomic RNA.

A distinct host cellular protein binding element was mapped within a 38-nucleotide (nt) sequence 166-129 nucleotides upstream of the 3' end of the MHV-JHM genome using a RNase T1 protection/gel mobility shift electrophoresis assay. The resultant RNA-protein complex contains six host cellular proteins, one protein of 120-kDa molecular mass, two poorly resolved species approximately 55 kDa in size, a second pair of poorly resolved 40-kDa proteins, and a minor component of 25 kDa. A series of RNA probes containing deletions or clustered transversion mutations were tested for their ability to form complexes with mock- and MHV-JHM-infected cytoplasmic extracts. Three mutant RNA probes (mA, mB, and mC) with deletions at 154-140, 139-129, and 128-118, respectively, expressed 4, 37, and 94% of the host protein binding activity exhibited by the wild-type RNA. Defective interfering (DI) RNAs (DImA, DImB, and DImC) containing corresponding deletions at 154-140, 139-129, 128-118, and another DI RNA (DImD) with a deletion at nucleotides (nts) 112-102, a region which did not affect RNA-protein interactions, were transfected into MHV-JHM-infected 17CL-1 cells to assay the effects of these mutations on DI RNA replication. All of these mutations had an adverse effect on DI RNA replication. However, analysis of negative strand mutant DI RNAs revealed that two mutants (DImC and DImD) carrying deletions having little or no effect on RNA-protein interaction in our RNA-protein binding assays maintained their mutant sequences. In contrast, the other two mutants (DImA and DImB) containing deletions that dramatically decreased RNA-protein binding activity did not maintain their mutations; wild-type sequences were restored in the majority of the progeny negative strand molecules. These data indicate that the 26-nucleotide sequence at positions 154-129 from the 3' end of viral genome is important to both RNA-protein binding and viral replication. This protein binding element contains an 11-nt sequence (UGAGAGAAGUU, positions 139-129) very similar to a more 3' sequence (UGAAUGAAGUU) previously implicated in host protein binding and viral RNA replication (Yu and Leibowitz, 1995a and 1995b).

Animals↗
PubMed1997

The development of morphine tolerance and dependence in rats with chronic pain.

The development of tolerance and dependence to morphine injected onto the spinal cord was examined in a model of chronic pain following spinal cord injury in rats. Intrathecal morphine completely relieved the marked pain-like response of these rats to innocuous mechanical stimuli. The analgesic effect of morphine injected twice daily was, however, diminished within a few days. Tolerance to the antinociceptive effect of morphine assessed with the tail flick test also developed similarly in rats with chronic pain and in normal controls. Both groups exhibited similar signs of naloxone-precipitated withdrawal after 3 weeks of morphine treatment. The results suggest that the presence of chronic pain-like behavior did not prevent the development of morphine tolerance and dependence, even when morphine was used to treat the chronic pain itself.

Animals↗
PubMed1997

Reduction in surface urokinase receptor forces malignant cells into a protracted state of dormancy.

Considerable evidence links urokinase plasminogen activator (uPA) bound to its surface receptor (uPAR) with enhanced invasiveness of cancer cells. By blocking uPAR expression in human epidermoid carcinoma cells (HEp3), we have now identified an additional and novel in vivo function for this receptor by showing that receptor-deficient cells enter a state of dormancy reminiscent of that observed in human cancer metastasis. Its main characteristic is survival without signs of progressive growth. Five clones transfected with a vector expressing uPAR antisense RNA under the beta-actin promoter were isolated and shown to have uPAR (at the mRNA and protein levels) reduced by 50 to 80%; four clones, transfected with vector alone and having uPAR levels similar to those of parental cells, served as controls. In confirmation of our previous results, reduced uPAR always coincided with a significantly reduced invasiveness. Each of the control clones produced rapidly growing, highly metastatic tumors within 2 wk of inoculation on chorioallantoic membranes (CAMs) of chick embryos. In contrast, each of the clones with low surface uPAR, whose proliferation rate in culture was indistinguishable from controls, remained dormant for up to 5 mo when inoculated on CAMs. Thus, the reduction in uPAR altered the phenotype of HEp3 tumor cells from tumorigenic to dormant. Although protracted, tumor dormancy was not permanent since in spite of maintaining low uPAR levels, each of the in vivo-passaged antisense clones eventually reemerged from dormancy to initiate progressive growth and to form metastases at a level of 20 to 90% of that of fully malignant control. This observation suggested that other factors, whose expression is dependent on cumulative and prolonged in vivo effects, can compensate for the lack of a full complement of surface uPAR required for the expression of malignant properties. These "reemerged," uPAR-deficient clones were easily distinguishable from the vector-transfected controls by the fact that after only 1 wk in culture, the invasion of CAM by all five clones and tumorigenicity of four of the five clones were reduced back to the values observed before in vivo maintenance. In contrast, dissociated and in vitro-grown cells of control tumors were fully invasive and produced large, metastatic tumors when reinoculated on CAMs. Quantitation of the percent of apoptotic and S-phase cells in vivo, in the control and uPAR-deficient, dormant clones, showed that the mechanism responsible for the dormancy was a diminished proliferation.

Apoptosis↗
PubMed1997

Isolation and characterization of a structural homologue of human PRK2 from rat liver. Distinguishing substrate and lipid activator specificities.

A homologue of human protein kinase C (PKC)-related kinase-2, PRK2, which had previously escaped identification in normal mammalian tissues, was isolated from rat liver as the protease-activated kinase (PAK) originally named PAK-2. The 130-kDa cytosolic enzyme was purified to homogeneity and shown by tryptic peptide and reverse transcriptase- polymerase chain reaction (RT-PCR)-amplified rat cDNA sequence analyses to be structurally related to the 116-kDa rat hepatic PAK-1/protein kinase N (PKN) and, even more closely (95% sequence identity) to the 130-kDa human PKC-related kinase, PRK2. Rat myeloma RNA was used as the RT-PCR template because of its relative abundance in PAK-2/PRK2 mRNA compared with liver and other rat tissues. The catalytic properties of PAK-2/PRK2 in many respects resembled those of hepatic PAK-1/PKN, but were distinguished by more favorable kinetics with several peptide substrates, and greater sensitivity to PKC pseudosubstrate and polybasic amino acid inhibitors. PAK-2/PRK2 was also activated by lipids, particularly cardiolipin and to a lesser extent by other acidic phospholipids and unsaturated fatty acids. Cardiolipin activation was most evident with autophosphorylation and histone H2B phosphorylation, but only marginally evident with the favored ribosomal S6-(229-239) peptide substrate for the protease-activated kinase activity. It was concluded that PAK-2 is the rat homologue of human PRK2, with biochemical properties distinct from although overlapping those of the PAK-1/PKN/PRK1 isoform.

Amino Acid Sequence↗
PubMed1997

Pharmacokinetics of aztreonam in critically ill surgical patients.

The pharmacokinetics of aztreonam in critically ill surgical patients with serious gram-negative infections were studied. Blood samples were taken before and at 30 minutes, 2.5 hours, and 5 hours after a dose of aztreonam 2 g i.v. every six hours. All patients had received at least two aztreonam doses before the dosage interval being studied. Aztreonam concentrations were measured by high-performance liquid chromatography. Aztreonam's pharmacokinetics, the severity of illness, and patient outcomes were examined. A total of 28 patients with 111 serum aztreonam concentrations were included in the analysis. The patients were young (mean age, 35 years) and predominantly male. The mean APACHE II score was 19.3, and 22 patients had sepsis. Four patients died. The mean volume of distribution (V) of 0.35 L/ kg was nearly twice the previously reported steady-state value for healthy volunteers (0.18 L/kg) and was highly variable. A slightly higher than normal mean V, 0.22 L/ kg, was seen in a subset of six patients whose infection occurred earlier in their intensive care and who had lower APACHE II scores. While with some antibiotics the elevated V would imply difficulty in achieving therapeutic drug levels, 99 (89%) of the 111 concentrations were at or above the in vitro susceptibility breakpoint of 8 micrograms/mL. Despite observations of markedly increased and highly variable V in critically ill surgical patients, a standard dosage of aztreonam was usually sufficient to maintain adequate serum drug levels.

Adolescent↗
PubMed1997

Inhibition of a mitotic motor compromises the formation of dendrite-like processes from neuroblastoma cells.

Microtubules in the axon are uniformly oriented, while microtubules in the dendrite are nonuniformly oriented. We have proposed that these distinct microtubule polarity patterns may arise from a redistribution of molecular motor proteins previously used for mitosis of the developing neuroblast. To address this issue, we performed studies on neuroblastoma cells that undergo mitosis but also generate short processes during interphase. Some of these processes are similar to axons with regard to their morphology and microtubule polarity pattern, while others are similar to dendrites. Treatment with cAMP or retinoic acid inhibits cell division, with the former promoting the development of the axon-like processes and the latter promoting the development of the dendrite-like processes. During mitosis, the kinesin-related motor termed CHO1/MKLP1 is localized within the spindle midzone where it is thought to transport microtubules of opposite orientation relative to one another. During process formation, CHO1/ MKLP1 becomes concentrated within the dendrite-like processes but is excluded from the axon-like processes. The levels of CHO1/MKLP1 increase in the presence of retinoic acid but decrease in the presence of cAMP, consistent with a role for the protein in dendritic differentiation. Moreover, treatment of the cultures with antisense oligonucleotides to CHO1/MKLP1 compromises the formation of the dendrite-like processes. We speculate that a redistribution of CHO1/MKLP1 is required for the formation of dendrite-like processes, presumably by establishing their characteristic nonuniform microtubule polarity pattern.

Animals↗
PubMed1997

Effects of photostimulation on wound healing in diabetic mice.

BACKGROUND AND OBJECTIVE: Low-level laser irradiation at certain fluences and wavelengths can enhance the release of growth factors from fibroblasts and stimulate cell proliferation in vitro. We evaluated whether low-level laser irradiation can improve wound healing in diabetes mellitus. STUDY DESIGN/MATERIALS AND METHODS: Genetically diabetic mice (C57BL/Ksj/db/db) were used as the animal model for this wound healing study. The experimental animals were divided among four groups: negative control, positive control (topical basic fibroblast growth factor [bFGF] on wound), laser therapy group; and a combination group of laser therapy and topical bFGF. An argon dye laser (Lexel Auora Model 600) at a wavelength of 630 nm and an output of 20 m W/cm2 was used as the light source. The speed of wound closure and histological evaluation were used to analyze the experimental results. RESULTS: Laser irradiation enhanced the percentage of wound closure over time as compared to the negative control group (58.4 +/- 2.6 vs. 40.8 +/- 3.4 at day 10 and 95.7 +/- 2 vs. 82.3 +/- 3.6 at day 20, P < .01). Histological evaluation showed that laser irradiation improved wound epithelialization, cellular content, granulation tissue formation, and collagen deposition in laser-treated wounds as compared to the negative control group (6.4 +/- 0.16 vs. 3.8 +/- 0.13 at day 10 and 12 +/- 0.21 vs. 8.2 +/- 0.31, P < .01). CONCLUSION: This study of laser biostimulation on wound healing in diabetic mice suggests that such therapy may be of great benefit in the treatment of chronic wounds that occur as a complication of diabetes mellitus.

Administration, Topical↗
PubMed1997

Photo-irradiation improved functional preservation of the isolated rat heart.

BACKGROUND AND OBJECTIVE: Photo-irradiation causes a variety of effects in different cells and tissues. We hypothesized that photo-irradiation may improve cardiac preservation based on these observations. STUDY DESIGN/MATERIALS AND METHODS: For pre-storage treatment (Pre), the heart in an anesthetized open-chest rat was irradiated using an Argon-dye laser with a wavelength of 660 nm at a fluence of 16.8 J/cm2 or sham-operated. The heart was excised, perfused with Krebs-Henseleit Buffer, cardioplegically arrested, and stored by immersion at 0 degree C for 18 hrs. Functional recovery was evaluated by working reperfusion for 30 min. For post-storage treatment (Post), the isolated hearts were stored for 18 hrs at 0 degree C; laser irradiation at a fluence of 36 J/cm2 was administered during working reperfusion. Hearts which did not receive irradiation during reperfusion served as control. Furthermore, isolated cardiomyocytes were used to study laser effect on cellular ATP content, catalase activity, and nitric oxide (NO) release. RESULTS: Both Pre and Post groups showed significant improvement in recovery of aortic flow, cardiac output, and work compared to the corresponding control groups (P < 0.05). Combined Pre/Post laser treatment did not improve function. Investigation using isolated rat cardiomyocytes found that both end-storage ATP and end-reperfusion catalase activity in the laser-treated group were significantly higher than those in the untreated cells (P < 0.05). NO release increased by 15% in the laser group after 18 hrs of 37 degrees C incubation. CONCLUSION: Photo-irradiation improves functional recovery of the cold-stored rat heart possibly via conservation of ATP and antioxidant enzyme activity.

Adenosine Triphosphate↗
PubMed1997

Improvement of host response to sepsis by photobiomodulation.

BACKGROUND AND OBJECTIVE: Late sepsis causes immunosuppression and is associated with energy depletion in lymphocytes. Adjuvant treatment with ATP-MgCL2 appears to improve cellular energetics and decrease mortality. Laser irradiation can promote cell proliferation and increase cellular ATP synthesis, which may improve the host immune response in sepsis. The purpose of this study was to determine whether laser irradiation (LI) has a stimulatory effect on the immune response in sepsis using an animal model. STUDY DESIGN/MATERIALS AND METHODS: The cecal ligation and puncture (CLP) rat model was used. Thirty-six SD rats were divided equally among four groups: control (nonoperative), sham operation, CLP treated with laser irradiation, and CLP without laser irradiation. The peritoneal cavity of each animal in CLP/laser group was irradiated immediately after CLP using an Argon-dye laser at a wavelength of 630 nm and at a fluence of 5 J/cm2. Some animals were euthanized 24 hr following CLP and were used to evaluate the immune response (lymphocyte proliferation). In a separate experiment, the survival of septic rats was observed for 60 days. Lymphocytes isolated from normal rat spleens were used to observe for biostimulatory effects in vitro. RESULTS: LI significantly improved ex-vivo lymphocyte proliferation of cells from septic rats (179.7 +/- 17.2 vs. 129.5 +/- 7.8; P < 0.01) and enhanced survival in septic rats (79% vs. 42%; P < 0.001). LI significantly stimulated lymphocyte proliferation in the presence of mitogenic stimuli and enhanced lymphocyte ATP synthesis (P < 0.05). CONCLUSION: LI improves the host immune response and survival rate in sepsis in an animal model. Our studies suggest that LI may be useful as an adjuvant therapy for sepsis.

Adenosine Triphosphate↗
PubMed1997

Intrathymically injected hemopoietic stem cells can differentiate into all lineage cells in the thymus: differences between c-kit+ cells and c-kit < low cells.

To investigate whether hemopoietic stem cells (HSCs) can differentiate into all lineage cells even in the thymus, we injected two types of HSCs (c-kit+ and c-kit < low cells) obtained from C57BL/6 Ly5.1 mice directly into the thymus of 7.5 Gy-irradiated C57BL/6 Ly5.2 mice. When c-kit < low cells (low density/lineage-/CD71-/major histocompatibility complex class I high/Sca-1+/Thy-1low/ c-kit < low) were injected, donor-derived (Ly5.1) cells were detected on day 8 after intrathymic (i.t.) injection, and the number reached a maximum on day 24 after injection. Granulocytes and macrophages were also detected on day 8 after injection. However, B220+ B cells were observed on day 13. Eighteen days after i.t. injection, the injected lobes showed red color due to the synchronous development of erythroid cells. Histological studies revealed the development not only of erythroid lineage cells but also of megakaryocytes in the thymus. In contrast, when c-kit+ cells were injected, a significant number of donor-derived cells were detected on day 5 after i.t. injection (three days earlier than in the case of c-kit < low cell injection). The differentiation into erythroid lineage cells was also observed six days earlier than when c-kit < low HSCs were injected. These findings suggest that c-kit < low HSCs are more primitive than c-kit+ HSCs, although both can differentiate into all lineage cells after i.t. injection.

Animals↗
PubMed1997

Dynamic properties of monomeric insect erythrocruorin III from Chironomus thummi-thummi: relationships between structural flexibility and functional complexity.

We have investigated the kinetics of geminate carbon monoxide binding to the monomeric component III of Chironomus thummi-thummi erythrocruorin, a protein that undergoes pH-induced conformational changes linked to a pronounced Bohr effect. Measurements were performed from cryogenic temperatures to room temperature in 75% glycerol and either 0.1 M potassium phosphate (pH 7) or 0.1 potassium borate (pH 9) after nanosecond laser photolysis. The distributions of the low temperature activation enthalpy g(H) for geminate ligand binding derived from the kinetic traces are quite narrow and are influenced by temperature both below and above approximately 170 K, the glass transition temperature. The thermal evolution of the CO binding kinetics between approximately 50 K and approximately 170 K indicates the presence of some degree of structural relaxation, even in this temperature range. Above approximately 220 K the width of the g(H) progressively decreases, and at 280 K geminate CO binding becomes exponential in time. Based on a comparison with analogous investigations of the homodimeric hemoglobin from Scapharca inaequivalvis, we propose a link between dynamic properties and functional complexity.

Animals↗
PubMed1997

Concurrent comparison of endoluminal repair vs. no treatment for small abdominal aortic aneurysms.

UNLABELLED: Endoluminal repair of abdominal aortic aneurysms (AAA) requires the aneurysm to have a proximal neck of at least 1.5 cm between the renal arteries and the aneurysm. Therefore, there may be advantages in performing endoluminal repair in the early stages of aneurysm development. However, the results of endoluminal repair performed in patients with small aneurysms with favourable morphology are not known. The aim of this study was to determine whether a randomised trial of endoluminal repair vs. no treatment for small aneurysms would be justified by using a concurrent comparison of endoluminal repair vs. no treatment for AAA 5 cm or less in diameter in patients presenting to the same centre during a 4-year period. METHODS: Data on 117 patients presenting with AAA 5 cm or less in diameter were entered into a registry. The decision to perform endoluminal repair vs. no treatment was based on the patient's preference following surgical consultation and investigation by computed tomography. This study reports the mortality, morbidity and survival of patients presenting between June 1992 and August 1996. During this time 43 patients had endoluminal repair and 67 patients had no treatment for small AAA. Seven patients were unfit for any intervention. Despite patient selection for different management in each group, close analysis revealed that the groups were similar with regard to co-morbidities and risk factors, as well as age, sex, and size of aneurysm. Follow-up was by progress CT scanning and ranged from 1 to 51 months (mean 18 months (NT) and 22 months (ER)). RESULTS: Endoluminal repair failed in six of 43 patients (14%) and resulted in 11 (25%) local vascular complications. There were two perioperative deaths and one late death in this group. Twenty-one of 67 AAA (31%) patients in the no treatment group enlarged beyond 5 cm in diameter during the study period. There was one death from aneurysm rupture and one death from myocardial infarction in this group. CONCLUSIONS: The patients in the endoluminal repair group have gained an asset in having their aneurysms repaired at a cost of early morbidity following operation. These results suggest that a randomised trial of endoluminal repair vs. no treatment will become justified in the subset of patients with small AAA 5 cm or less, if the incidence of complications can be reduced by further improvements in endoluminal technology.

Age Factors↗
PubMed1997

Conversion from endoluminal to open repair of abdominal aortic aneurysms: a hazardous procedure.

AIM: The purpose of this study was to analyse the technical problems associated with conversion from endoluminal repair of abdominal aortic aneurysms (AAA) to open repair and document the outcome in patients with this clinical course. METHODS: Between May 1992 and May 1996 endoluminal repair of AAA was undertaken in 113 patients. Forty-eight of these had medical co-morbidities which led to them being rejected for open repair at other medical centres. Conversion from endoluminal to open repair was required in 18 patients. Thirteen of these occurred at the original operation (primary conversion) and five occurred at a later operation (secondary conversion). Seven of the 18 patients undergoing conversion had serious medical co-morbidities. Three different methods of open repair were used. The technique selected was determined by the cause of failure leading to conversion. Standard open AAA repair was used in patients requiring conversion for access problems (n = 2) and balloon malfunction, where the device ended up entirely within the aneurysmal sac (n = 1). Modifications to the standard technique were required in patients in which the endograft was correctly positioned immediately below the renal arteries and/or where part of the endograft was within one or both common iliac arteries (n = 11). Supra-coeliac control was required for patients with aortic rupture (n = 1), renal arteries covered by the endograft (n = 2) and situations where the delivery catheter was trapped within the aorta above a twisted bifurcated graft (n = 1). The mean volume of contrast used was 225 ml and the mean operative time was 5.25 h in patients undergoing primary conversion. RESULTS: Conversion to open repair was achieved in all 18 patients. Renal impairment requiring dialysis occurred in three patients. There were three perioperative deaths, all of which were procedure-related (17%), and one late death. All four deaths occurred from among the group of seven patients with preoperative co-morbidities. CONCLUSIONS: Converting an endoluminal to an open AAA repair may require modifications to the standard open technique and result in a much higher than generally accepted morbidity and mortality rate. Patients rejected for open repair because of co-morbidities ran the same chance of requiring conversion as those without co-morbidities (15-17%). If conversion was required, however, they stood a 3 in 7 or 43% chance of dying.

Aged↗
PubMed1997

Comparison of the anti-allodynic and antinociceptive effects of systemic; intrathecal and intracerebroventricular morphine in a rat model of central neuropathic pain.

The present study has assessed the efficacy and potency of systemic, intrathecal (i.t.) and intracerebroventricular (i.c.v.) morphine in alleviating a chronic mechanical allodynia-like behaviour in a rat model of central pain after spinal cord injury. The anti-allodynic potency of morphine was compared to its antinociceptive potency in both spinally injured and normal rats. Systemic (intraperitoneal or subcutaneous) morphine did not significantly relieve allodynia up to 3 mg/kg cumulative dose, which was sedative. Mechanical allodynia-like behaviour was only significantly relieved by l0 mg/kg morphine which caused severe sedation. Low doses of i.c.v. morphine abolished vocalization of allodynic rats to von Frey hair stimulation. However, other components of abnormal reactions to innocuous mechanical stimulation, such as agitation, jumping and avoidance, were only relieved by i.c.v. morphine at high, sedative doses. In contrast, i.t. morphine dose dependently reversed all components of the allodynic reactions without causing sedation. Morphine administered by all three routes produced powerful antinociception in the tail flick test in normal rats. The antinociceptive potency of morphine was reduced after systemic, i.t. and, particularly, i.c.v. administration in allodynic rats. These results indicated that i.t. morphine relieved the mechanical allodynia-like responses in spinally injured rats, whereas systemic or i.c.v. morphine only increased the response threshold to innocuous mechanical stimulation at high doses, which was associated with sedation, making it difficult to assess the anti-allodynic effect. However, i.c.v. morphine may be particularly effective for the affective component of pain in the present model. The antinociceptive potency of morphine was also reduced in spinally injured rats. It is suggested that morphine may be differentially effective against different types of pain after different routes of administration. Spinal morphine may be a therapeutic alternative in treating central pain after spinal cord injury.

Journal Article↗