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Biomedical subjects

M Maley

Publications and source records attributed to M Maley.

At least 19 recordsLinked to original sources

Development of a real time RT-PCR to detect and type ovine pestiviruses.

A real time one-step RT-PCR was designed to detect and type border disease virus (BDV), bovine viral diarrhea virus (BVDV) type 1 and BVDV type 2 in ovine samples. The real time RT-PCR was shown to behave in a linear manner and had limits of detection of 100-1000 copies of viral RNA as judged by in vitro transcribed RNA. The real time RT-PCR was validated on 50 clinical samples from UK flocks and was more sensitive than a virus isolation and a classical nested RT-PCR (nRT-PCR). The results of real time RT-PCR virus typing agreed completely with sequencing. The majority of ovine isolates were BDV; a small proportion were BVDV type 1. BVDV type 2 was not detected in any sample. This test appears reliable and can be used for the typing of ovine pestiviruses in the UK.

Animals↗

The incidence of red cell alloantibodies underlying panreactive warm autoantibodies.

A recognized hazard of administering blood transfusions to patients with panreactive warm autoantibodies is that alloantibodies may be masked. Studies have shown the incidence of underlying alloantibodies to be 30 to 40 percent. Adsorption procedures can be used to remove autoantibodies and allow detection and identification of underlying alloantibodies. This study contains data from 126 patients referred to the Red Cell Immunohaematology laboratory at the National Blood Service, Newcastle upon Tyne, United Kingdom. These patients were from the northeast of England, a population for which data have not previously been reported. Samples identified as containing panreactive warm autoantibodies were subjected to adsorption procedures (95 by alloadsorption and 31 by autoadsorption). Absorbed sera were then tested to identify underlying alloantibodies. Of 126 samples, 39 (31%) contained a total of 61 RBC alloantibodies; 15 (12%) contained 2 or more antibody specificities; and 14 (11%) contained alloantibodies not found within the Rh or Kell blood group systems. Antibodies identified included the following specificities: E (19), D (9), c (7), C (6), S (5), Fy(a) (3), Jk(a) (2), Jkb (2), K (2),Kp(a) (2), Fy(b),C(w),N, and f (ce). This study reinforces the value of adsorption studies, whether using autologous or allogeneic RBCs, when panreactive warm autoantibodies are present. In addition, this study confirms that it is not appropriate in these cases simply to issue blood which is "least incompatible" or Rh phenotype- and K antigen-matched.

Autoantibodies↗

The impact of pan-resistant bacterial pathogens on survival after lung transplantation in cystic fibrosis: results from a single large referral centre.

Reported actuarial one-year survival for patients with cystic fibrosis (CF) after lung transplant is 55-91%. Infection is the most common cause of early death. Colonization with Burkholderia cepacia complex is associated with reduced survival and international lung transplant referral guidelines support individual unit assessment policies for patients colonized with other pan-resistant bacteria. We examined local data on survival after transplant for CF to determine the impact of colonization with pan-resistant bacteria. A retrospective review of all CF patients from Royal Prince Alfred Hospital (RPAH), Sydney, who underwent lung transplantation at St Vincent's Hospital, Sydney, 1989-2002, was performed. Sixty-five patients were listed for lung transplantation with 54 (male: female=29:25) receiving transplants. Of the 11 patients (17%) who died on the waiting list, six were colonized with pan-resistant Pseudomonas aeruginosa. Thirty of the 54 transplanted patients had at least one pan-resistant organism before transplant. In 28 this included P. aeruginosa. Overall one-year survival was 92% with a median survival of 67 months. Overall survival for the pan-resistant group (N = 30) was not significantly different to survival in those with sensitive organisms (N = 24) (Logrank chi square = 1.6, P = 0.2). Three patients colonized with B. cepacia complex pre-transplant survive at 11, 40 and 60 months post-transplant. Infection contributed to 11 of the 18 post-transplant deaths, with pre-transplant-acquired bacterial pathogens responsible in two cases. Patients continued to acquire multiresistant bacteria post-transplantation. Lung transplant survival at St Vincent's Hospital for CF adults from RPAH compares favourably with international benchmarks. Importantly, colonization with pan-resistant bacteria pre-transplant did not appear to adversely affect survival post-transplant.

Adult↗

Intrinsic pinning of vortices as a direct probe of the nonuniform Larkin-Ovchinnikov-Fulde-Ferrell state in layered superconductors.

Previously the search for the modulated superconducting Larkin-Ovchinnikov-Fulde-Ferrell (LOFF) state was performed by means of measurements which do not give direct information on spatial modulation of the superconducting state. We propose to measure interlayer conductivity in Josephson-coupled layered superconductors as a function of the strength and the orientation of the parallel magnetic field. We show that interlayer critical current and the conductivity have peaks when the magnetic field is perpendicular to the in-plane wave vector of the LOFF state and when the period of the Josephson vortex lattice induced by the magnetic field is commensurate with the LOFF period.

Journal Article↗

New superconducting phases in field-induced organic superconductor lambda-(BETS)2FeCl4.

We derive the parallel upper critical field, Hc2, as a function of the temperature T in quasi-2D organic compound lambda-(BETS)2FeCl4, accounting for the formation of the nonuniform Larkin-Ovchinnikov-Fulde-Ferrell (LOFF) state. To further check the 2D LOFF model, we propose to study the Hc2(T) curve at low T in tilted fields, where the vortex state is described by the high Landau level functions characterized by the index n. We predict a cascade of first-order transitions between vortex phases with different n, between phases with different types of the symmetry at given n and the change of the superconducting transition from the second order to the first order as FeCl4 ions are replaced partly by GaCl4 ions.

Journal Article↗

Identification and quantification of anti-D, -C and -G in alloimmunized pregnant women.

Our objectives were to investigate possible overestimation of maternal anti-D due to co-existing anti-C and/or anti-G, and to confirm the presence of anti-D in plasma presumed to contain anti-D+C. We investigated 96 samples (from 22 antenatal patients and 74 blood donors) initially identified as containing anti-D+C using routine investigation procedures. Anti-D quantification was performed using an Astoria Pacific International 300 (API 300) continuous flow analyser with R1R1 and R2R2 reagent red cells. Where possible, samples were tested manually using a rare D+, C-, G- cell, to confirm the presence of anti-D. Fifty-two of 96 samples (11/22 antenatal patients and 41/74 blood donors) gave >50% higher anti-D quantification results with R1R1 cells than with R2R2 cells. Anti-D was not detected using manual techniques in 16 of 73 samples tested (10/22 antenatal patients and 6/51 blood donors). Anti-D quantification using R1R1 reagent red cells may cause inaccurate estimation of anti-D levels, when anti-C and/or anti-G are present. Indeed, a significant number of cases, where apparent anti-D+C is identified, may contain only anti-C+G and lack an anti-D component. This may in turn lead to a failure to administer prophylactic anti-D immunoglobulin to RhD negative patients in cases where anti-D is not present, putting these patients at risk from immunization with possible consequences to future pregnancies.

Blood Grouping and Crossmatching↗

Development and clinical assessment of an artificial cornea.

Keratoprosthesis research has been a gradual, rather fragmentary process with advances being made by isolated groups of researchers. This has arisen partly because of poor funding in the area; research groups which have achieved commercial support have often had constraints upon the full disclosure of their findings. Despite these difficulties there has been real progress over the last decade by several independent groups. This article concentrates upon our own development of a hydrogel core-and-skirt keratoprosthesis, the Chirila KPro, in order to illustrate the scientific and clinical problems common to keratoprosthesis research. Pilot data from a clinical trial is presented and the priorities for future research are discussed.

Animals↗

Expression of laminin alpha1, alpha2, alpha4, and alpha5 chains, fibronectin, and tenascin-C in skeletal muscle of dystrophic 129ReJ dy/dy mice.

The dy/dy mouse is an animal model for human merosin-negative congenital muscular dystrophy (CMD), which has been reported to have reduced or no expression of the basement membrane protein laminin alpha2. We here investigate various myogenic and nonmyogenic tissues of mature dy/dy and control 129ReJ mice histologically and for laminin alpha2 expression. In addition, expression patterns of laminin alpha1, alpha2, alpha4, and alpha5 chains, the interstitial proteins fibronectin and tenascin-C, and the adhesion molecules VCAM-1, ICAM-1, and alpha4 integrin were characterized in skeletal muscle of 1- and 7-day and mature (>6 weeks old) dy/dy and control 129ReJ mice. The laminin alpha2 chain remained detectable in myogenic tissues of dy/dy mice by immunofluorescence using two different monoclonal antibodies and by Northern blot analysis. However, laminin alpha2 expression was significantly reduced or not detectable in nonmyogenic tissues of dy/dy mice, including skin, lung, kidney, brain, thymus, and eye. Focal lesions were observed in mature skeletal muscle only, characterized by necrotic tissue, isolated VCAM-1- and ICAM-1-positive cells indicative of inflammatory processes, and regenerating muscle fibers surrounded by intense tenascin-C and fibronectin expression. In contrast to studies on human CMD muscle, laminin alpha1 was not detectable in either dy/dy or control skeletal muscle using immunofluorescence or Northern blot analysis. Immunofluorescence localized laminin alpha4 to basement membranes of blood vessels, the endoneurium of the intramuscular nerves, and the neuromuscular junction in skeletal muscle of 1- and 7-day-old dy/dy and control mice. In mature muscle, laminin alpha4 expression shifted to the perineurium of intramuscular nerves in both dy/dy and control mice. Furthermore, strong upregulation of laminin alpha4 in the basement membranes of blood vessels, the perineurium of intramuscular nerves, and of isolated regenerating muscle fibers in the dy/dy mice was apparent. Investigation of 1-day-old animals revealed expression of laminin alpha5 in skeletal muscle fiber basement membranes of dy/dy but not control animals. This difference between dy/dy and control animals was no longer apparent at 7 days after birth, indicating a temporary shift in expression pattern of laminin alpha5 in dy/dy animals. Analysis of the extracellular matrix components of 1- and 7-day-old dy/dy and control skeletal muscle revealed an early onset of the dystrophy, even before histopathological features of the disease were evident. Our data confirm the absence of laminin alpha1 chain in myogenic tissues of both dy/dy and control mice and suggest compensation for reduced laminin alpha2 in dy/dy skeletal muscle by laminin alpha4 and, in early development, also laminin alpha5. These results have significant ramifications in the diagnosis of human merosin-negative CMD.

Age of Onset↗

Nurse complementary therapists. A return to healing.

As chronically ill patients take more responsibility for their own health and well-being, they are requesting information about complementary and alternative treatment options. Through training in complementary care techniques, nurses can better serve such clients.

Chronic Disease↗

Rapid death of injected myoblasts in myoblast transfer therapy.

Myoblast transplantation has been proposed as a potential therapy for Duchenne muscular dystrophy (DMD). A Y-chromosome-specific probe was used to track the fate of donor male myoblasts injected into dystrophic muscles of female mdx mice (which are an animal model for DMD). In situ analysis with the Y-probe showed extremely poor survival of isolated normal male (C57B1/10Sn) donor myoblasts after injection into injured or uninjured muscles of dystrophic (mdx) and normal (C57B1/10Sn) female host mice. A decrease in the numbers of donor (male) myoblasts was seen from 2 days and was marked by 7 days after injection: few or no donor myoblasts were detected in host muscles examined at 3-12 months. There was limited movement of the injected donor myoblasts and fusion into host myofibers was rare. The results of this study strongly suggest that the failure of clinical trials of myoblast transplantation in boys with DMD may have been due to rapid and massive death of the donor myoblasts soon after myoblast injection.

Animals↗

Protective effect of the 5-lipoxygenase inhibitor AA-861 on cerebral edema after transient ischemia.

This study examined the effect of AA-861, a specific 5-lipoxygenase inhibitor, on brain levels of leukotriene C4 (LTC4) and correlated any changes with changes in edema formation and cerebral blood flow (CBF) after transient ischemia in gerbils. Brain levels of LTC4 were observed to be increased at 1, 2, and 6 hours of reperfusion following 20 minutes of occlusion. At 2 hours of reperfusion, a pretreatment dose of 1000 mg/kg of AA-861 was required to inhibit more than 90% of the reperfusion-induced increases in brain LTC4. At this dose, inhibition of LTC4 production was observed at 2 and 6 hours of reperfusion. The specific gravity of both the cortex and subcortex was decreased at 6 hours of reperfusion after 20 minutes of occlusion. At 2 hours of reperfusion, no significant difference was observed in the specific gravity of the cortex and subcortex regions of gerbils pretreated with AA-861 or with vehicle, but at 6 hours of reperfusion significant positive differences were observed. Cerebral blood flow decreased to approximately 10% of preocclusion values during occlusion and returned to near-preocclusion values after 10 minutes of reperfusion. No significant differences were observed in regional CBF in the AA-861- and vehicle-pretreated gerbils during reperfusion. These findings indicate that LTC4 production after transient cerebral ischemia may be an important contributor to the development of cerebral edema and that CBF does not mediate the LTC4-involved development of edema.

Animals↗

Primary total hip reconstruction with a titanium fiber-coated prosthesis inserted without cement.

A prospective study was done of the intermediate-term clinical and radiographic results of 121 total hip arthroplasties in which a Harris-Galante porous titanium-fiber-coated prosthesis was inserted without cement in 110 patients. The average age at the time of the operation was forty-nine years (range, twenty to seventy years). The average duration of follow-up was sixty-seven months (range, fifty-five to seventy-nine months). The average preoperative Harris hip score was 55 points, and the average postoperative score was 93 points. One acetabular component was revised due to recurrent dislocation. Eleven femoral implants were unstable, and of these, four were revised. Cortical erosion was present around the distal part of the femoral stem in nine patients (8 per cent) who had stable implants, and one of these femoral implants was revised because the erosion was extensive. Survivorship analysis at five years revealed a 97 per cent chance of survival (95 per cent confidence limit, 0.937 to 1.0) of the Harris-Galante femoral-stem implant inserted without cement.

Acetabulum↗

Relationship between plasma glucose, brain lactate, and intracellular pH during cerebral ischemia in gerbils.

The dose-response relation between plasma glucose and brain lactate and the relation of these parameters to intracellular pH during severe cerebral ischemia have not been well characterized over a wide range of plasma glucose levels. Experiments to delineate these relations in the gerbil model of global ischemia were performed by using phosphorus-31 nuclear magnetic resonance spectroscopy to measure intracellular pH and a new method to measure brain lactate. Ischemia increased final brain lactate linearly 4 mumol/g for every 100 mg/dl increase in plasma glucose up to 650 mg/dl (p = 0.0001, r2 = 0.9); beyond 650 mg/dl, saturation of the glucose transport-glycolysis system occurred. Plasma glucose correlated better with ischemic intracellular pH than did brain lactate. However, when brain lactate levels are compared with intracellular pH during ischemia, the relation may be threshold rather than linear. A narrow transition zone, during which ischemic intracellular pH decreased precipitously with increasing brain lactate, was observed between 17 and 22 mumol/g; below 17 mumol/g, intracellular pH remained stable at 6.8-6.9, whereas above 22 mumol/g, intracellular pH decreased maximally to about 6.2. The marked decrease in intracellular pH that occurs when brain lactate surpasses 17 mumol/g suggests that this sudden drop in intracellular pH may account for the "lactate threshold" for increased cerebral ischemic damage.

Analysis of Variance↗