Search PubMed⌕ Search

Biomedical subjects

J Murray

Publications and source records attributed to J Murray.

At least 37 records · Page 2Linked to original sources
PubMed2001

Galantamine: a randomized, double-blind, dose comparison in patients with Alzheimer's disease.

OBJECTIVES: To investigate whether Galantamine significantly improves the core symptoms of Alzheimer's disease (AD). BACKGROUND: Galantamine is a reversible, competitive, selective inhibitor of acetylcholinesterase (AChE) that also allosterically modulates nicotinic acetylcholine receptors. This dual mechanism of action provided the rationale for a phase II trial of galantamine in AD. METHOD: A multicentre, randomized, parallel, double-blind, placebo-controlled trial was carried out to evaluate the efficacy and tolerability of galantamine 18, 24 and 36 mg/day administered for 3 months in 285 patients with mild-to-moderate probable AD. The primary outcome measure was the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog); secondary outcome measures were the Clinical Global Impression of Change (CGIC) and the Progressive Deterioration Scale (PDS). RESULTS: Patients treated with galantamine 24 mg/day had a significantly better outcome than placebo on ADAS-cog; the treatment difference was 3 points on the intention-to-treat (ITT) analysis ( p = 0.01) and 4.2 points on per protocol analysis ( p = 0.001). Per protocol analysis showed that galantamine had a significantly better outcome than placebo on PDS ( 24-mg/day dose, p < 0.05) and CGIC (36-mg/day dose, p < 0.05). Galantamine was well tolerated at the lower doses of 18 and 24 mg/day where it produced mild, transient effects typical of cholinomimetic agents. CONCLUSION: This study shows that, relative to placebo, galantamine significantly improves the core symptoms of Alzheimer's disease.

Aged↗
PubMed2001

Expression of vascular endothelial growth factor receptors in smooth muscle cells.

Vascular Endothelial Growth Factor (VEGF) has been typically considered to be an endothelial-specific growth factor. However, it was recently demonstrated that VEGF can interact with non endothelial cells. In this study, we tested whether vascular smooth muscles cells (VSMCs) can express VEGF receptors, such as flk-1, flt-1, and neuropilin (NP)-1, and respond to VEGF in vitro. In cultured VSMCs, flk-1 and flt-1 expression was inversely related to cell density. The expression of flk-1 was down-regulated with increasing passage numbers. However, NP-1 levels were not affected by cell density or passage numbers. Flk-1, Flt-1, and NP-1 protein levels were confirmed by Western Blotting. Although the functional mature form of Flk-1 protein is expressed at low levels in VSMCs, phosphorylation of Flk-1 following VEGF(165) stimulation was still observed. SMCs migrated significantly in response to VEGF(165) and VEGF-E, whereas Placenta Growth Factor (PlGF) induced migration only at higher concentrations. Since VEGF-E is a specific activator of flk-1 while PlGF specifically activates only flt-1, SMC migration induced by VEGF(165) is likely to be mediated primarily through the flk-1 receptor. VSMCs did not significantly proliferate in response to VEGF(165), PlGF, and VEGF-E. In conclusion, our studies demonstrate the presence of VEGF receptors on VSMCs that are functional. These studies also indicate that in vivo, VEGF may play a role in modulating the response of VSMCs.

Animals↗
PubMed2001

Descriptive information about Down syndrome: a content analysis of serum screening leaflets.

It is recommended practice that prior to prenatal screening, women receive information about the condition(s) being tested for. The present study critically evaluated information about Down syndrome as contained in 80 leaflets provided to pregnant women in the UK prior to serum screening. First, a content analysis by information type was conducted to give an overall picture of the material provided. Second, the image of the condition as conveyed by the content was analysed and compared with a similar study of cystic fibrosis (CF) screening leaflets. The majority of information (89%) was of a medico-clinical nature, with 11% addressing other issues associated with Down syndrome. The median number of sentences describing the condition was one, with 33% of the leaflets containing no descriptive information. Overall, a negative image of Down syndrome was conveyed by the leaflets, which contrasted with a more neutral image of CF in the comparison study. In order to facilitate informed choices, more attention should be paid to providing women with information about Down syndrome prior to serum screening. Such information needs to be more balanced in its construction, with thought given to the needs of the reader, and to the tone and the content of the message conveyed.

Cystic Fibrosis↗
PubMed2001

Reliable variables in the exsanguinated patient which indicate damage control and predict outcome.

BACKGROUND: Exsanguination as a syndrome is ill defined. The objectives of this study were to investigate the relationship between survival and patient characteristics--vital signs, factors relating to injury and treatment; determine if threshold levels of pH, temperature, and highest estimated blood loss can predict survival; and identify predictive factors for survival and to initiate damage control. MATERIAL AND METHODS: A retrospective 6-year study was conducted, 1993 to 1998. In all, 548 patients met one or more criteria: (1) estimated blood loss > or =2,000 mL during trauma operation; (2) required > or =1,500 mL packed red blood cells (PRBC) during resuscitation; or (3) diagnosis of exsanguination. Analysis was made in two phases: (1) death versus survival in emergency department (ED); (2) death versus survival in operating room (OR). Statistical methods were Fisher's exact test, Student's t test, and logistic regression. RESULTS: For 548 patients, mean Revised Trauma Score 4.38, mean Injury Severity Score 32. Penetrating injuries 82% versus blunt injuries 18%. Vital statistics in emergency department: mean blood pressure 63 mm Hg, heart rate 78 beats per minute. Mean OR pH 7.15 and temperature 34.3 degrees C. Mortality was 379 of 548 (69%). Predictive factors for mortality (means): pH < or =7.2, temperature <34 degrees C, OR blood replacement >4,000 mL, total OR fluid replacement >10,000 mL, estimated blood loss >15 mL/minute (P <0.001). Analysis 1: death versus survival in ED, logistic regression. Independent risk factors for survival: penetrating trauma, spontaneous ventilation, and no ED thoracotomy (P <0.001; probability of survival 0.99613). Analysis 2: death versus survival in OR, logistic regression. Independent risk factors for survival: ISS < or =20, spontaneous ventilation in ED, OR PRBC replacement <4,000 mL, no ED or OR thoracotomy, absence of abdominal vascular injury (P <0.001, max R(2) 0.55, concordance 89%). CONCLUSIONS: Survival rates can be predicted in exsanguinating patients. "Damage control" should be performed using these criteria. Knowledge of these patterns can be valuable in treatment selection.

Adolescent↗
PubMed2001

Immune evasion genes from filarial nematodes.

Helminth parasites have large genomes (approximately 10(8) bp) which are likely to encode a spectrum of products able to block or divert the host immune response. We have employed three parallel approaches to identify the first generation of 'immune evasion genes' from parasites such as the filarial nematode Brugia malayi. The first strategy is a conventional route to characterise prominent surface or secreted antigens. In this way we have identified a 15-kDa protein, which is located on the surface of both L3 and adult B. malayi, and secreted by these parasites in vitro, as a member of the cystatin (cysteine protease inhibitor) family. This product, Bm-CPI-2, blocks conventional cysteine proteases such as papain, but also the aspariginyl endopeptidase involved in the Class II antigen processing pathway in human B cells. In parallel, we identified the major T cell-stimulating antigen from the microfilarial stage as a serpin (serine protease inhibitor), Bm-SPN-2. Microfilariae secrete this product which blocks two key proteases of the neutrophil, a key mediator of inflammation and innate immunity. The second route involves a priori hypotheses that helminth parasites encode homologues of mammalian cytokines such as TGF-beta which are members of broad, ancient metazoan gene families. We have identified two TGF-beta homologues in B. malayi, and shown that one form (Bm-TGH-2) is both secreted by adult parasites in vitro and able to bind to host TGF-beta receptors. Likewise, B. malayi expresses homologues of mammalian MIF, which are remarkably similar in both structure and function to the host protein, even though amino acid identity is only 28%. Finally, we deployed a third method of selecting critical genes, using an expression-based criterion to select abundant mRNAs taken from key points in parasite life histories. By this means, we have shown that the major transcript present in mosquito-borne infective larvae, Bm-ALT, is a credible vaccine candidate for use against lymphatic filariasis, while a second abundantly-expressed gene, Bm-VAL-1, is similar to a likely vaccine antigen being developed against hookworm parasites.

Animals↗
PubMed2001

Expression and immune recognition of Brugia malayi VAL-1, a homologue of vespid venom allergens and Ancylostoma secreted proteins.

Several important nematode parasites have been found to express members of a gene family variously termed as venom allergen antigen homologue (vah) or Ancylostoma secreted protein (asp). In some cases these products are secreted by infective larval stages and have been suggested to be effective vaccine immunogens. We isolated the corresponding gene from the human filarial nematode, Brugia malayi, by first searching the expressed sequence tag (EST) dataset generated by the Filarial Genome Project and then using gene-specific nondegenerate primers matching the selected gene for PCR, from B. malayi cDNA libraries. We report here the full-length gene sequence, which we have designated as Bm-val-1, for vah/asp-like. The corresponding protein (Bm-VAL-1) contains 232 amino acids in a single homology unit, unlike products from some other species in which there is a tandem repeat. A putative signal sequence is present at the 5' end and there are two potential N-glycosylation sites. Murine antibodies to recombinant Bm-VAL-1 react with a 28 kDa protein in L3 extracts and recombinant Bm-VAL-1 is recognised by murine T cells primed with soluble L3 proteins. Of 82 ESTs corresponding to Bm-val-1, 72 are recorded from the infective larval (L3) stage. However, PCR on the first-strand cDNA from later mammalian stages revealed some expression at most subsequent time points. Over 95% (20/21) of microfilaraemic human filariasis patients are seropositive for antibodies to Bm-VAL-1, with particularly high levels of IgG3 and IgG4 isotypes. The IgG4 subclass may indicate stimulation by adult and/or microfilarial-derived immunogens. The association of Bm-VAL-1 with the infective stage and its recognition by humans exposed to filariasis suggests that further evaluation of this antigen as a vaccine candidate should be performed.

Adult↗
PubMed2001

Mapping of 13 horse genes by fluorescence in-situ hybridization (FISH) and somatic cell hybrid analysis.

We report fluorescence in-situ hybridization (FISH) and somatic cell hybrid mapping data for 13 different horse genes (ANP, CD2, CLU, CRISP3, CYP17, FGG, IL1RN, IL10, MMP13, PRM1, PTGS2, TNFA and TP53). Primers for PCR amplification of intronic or untranslated regions were designed from horse-specific DNA or mRNA sequences in GenBank. Two different horse bacterial artificial chromosome (BAC) libraries were screened with PCR for clones containing these 13 Type I loci, nine of which were found in the libraries. BAC clones were used as probes in dual colour FISH to confirm their precise chromosomal origin. The remaining four genes were mapped in a somatic cell hybrid panel. All chromosomal assignments except one were in agreement with human-horse ZOO-FISH data and revealed new and more detailed information on the equine comparative map. CLU was mapped by synteny to ECA2 while human-horse ZOO-FISH data predicted that CLU would be located on ECA9. The assignment of IL1RN permitted analysis of gene order conservation between HSA2 and ECA15, which identified that an event of inversion had occurred during the evolution of these two homologous chromosomes.

Animals↗
PubMed2001

Quinolone resistance in neutropenic patients: the effect of prescribing policy in the UK and Pakistan.

Quinolones are increasingly used as prophylaxis in neutropenic patients to prevent serious Gram-negative septicaemias but practice is not uniform because of the controversial evidence as to their effectiveness. It is unclear if they are of real benefit in patients with short episodes of neutropenia such as those resulting from treatment for solid tumours and lymphomas. The concern over the use of ciprofloxacin in such settings is the increasing development of quinolone resistant Gram-negative bacteria. We have retrospectively analysed our bacterial isolate resistance patterns in the Queen Elizabeth Hospital (QE) and in the Haematology Department of the Aga Khan Hospital (AKU), Pakistan where all patients would receive ciprofloxacin prophylaxis when neutropenic. Seven out of 57 (12.2%) and 18 out of 55 (32.7%) Gram-negative organisms isolated from blood cultures at the QE and AKU Haematology Departments, respectively, were resistant to ciprofloxacin (P < 0.01). In the Birmingham community this was significantly lower (P < 0.01) (55 out of 6423: 0.85%). We also showed a higher level of E. coli resistance at the AKU (18 out of 31: 58%) where ciprofloxacin use was more widespread than at the QE (1 out of 11, P < 0.01). We conclude that ciprofloxacin should not be used indiscriminately.

Anti-Infective Agents↗
PubMed2001

Liberalized screening for blunt carotid and vertebral artery injuries is justified.

BACKGROUND: Current literature suggests that blunt carotid injuries (BCIs) and vertebral artery injuries (BVIs) are more common than once appreciated. Screening criteria have been suggested, but only one previous study has attempted to identify factors that predict the presence of BCI/BVI. This current study was conducted for two reasons. First, we wanted to determine the incidence of BCI/BVI in our institution. Second, we wanted to determine the incidence of abnormal four-vessel cerebral angiograms ordered for injuries and signs believed to be associated with BCI/BVI and thus to determine whether the screening protocol developed was appropriate. METHODS: From August 1998, we used liberalized screening criteria for patients who were prospectively identified and suspected to be at high risk for BCI/BVI if any of the following were present: anisocoria, unexplained mono-/hemiparesis, unexplained neurologic exam, basilar skull fracture through or near the carotid canal, fracture through the foramen transversarium, cerebrovascular accident or transient ischemic attack, massive epistaxis, severe flexion or extension cervical spine fracture, massive facial fractures, or neck hematoma. Four-vessel cerebral angiograms were used for screening for BCI/BVI. RESULTS: Over the 18-month study period, 48 patients were angiographically screened, with 21 patients (44%) being identified as having a total of 19 BCIs and 10 BVIs. Nine patients had unilateral carotid artery injuries and three patients had bilateral carotid artery injuries. Vertebral artery injuries were unilateral in six patients. One patient had bilateral carotid artery injuries and a unilateral vertebral artery injury. One patient had a unilateral carotid artery injury and a unilateral vertebral artery injury, and one patient had a unilateral carotid artery injury and bilateral vertebral artery injuries. During the same study period, 2,331 trauma patients were admitted, with 1,941 (83%) secondary to blunt trauma. The overall incidence of BCI/BVI was 1.1%. The frequency of abnormal angiograms ordered for cerebrovascular accident or transient ischemic attack, massive epistaxis, or severe cervical spine fractures was 100%. The frequency of abnormal angiograms ordered for the other indications was as follows: fracture through foramen transversarium, 60%; unexplained mono- or hemiparesis, 44%; basilar skull fracture, 42%; unexplained neurologic examination, 38%; anisocoria, 33%; and severe facial fractures, 0%. CONCLUSION: The liberalized screening criteria used in this study were appropriate to identify patients with BCI/BVI. This study suggests BCI/BVI to be more common than previously believed and justifies that screening should be liberalized.

Adolescent↗
PubMed2001

Cystic fibrosis and fragile X syndrome: the arguments for antenatal screening.

The ultimate public health aim of genetic screening is prevention. This can be achieved by reducing birth prevalence through primary or secondary methods such as pre-conceptional or antenatal screening. Tertiary prevention by neonatal screening is also an option where there is direct unbiased evidence for a substantial improvement in prognosis. In addition to this, the information provided during screening is also of value, enabling individuals to make choices that otherwise would not have been available. Having elucidated the natural histories and genetic defects underlying two common, serious genetic disorders, cystic fibrosis and fragile X syndrome, considerable efforts have been channelled into ascertaining the most efficacious method of prevention. To date there is only indirect evidence to suggest that neonatal screening improves prognosis in cystic fibrosis. Similarly, treatment for fragile X syndrome is limited and therefore early identification of the disorder by neonatal screening is unlikely to improve long term outlook. Thus the focus of this review is on primary and secondary preventive methods.

Animals↗
PubMed2001

Power Doppler ultrasound assessment of rheumatoid hand synovitis.

OBJECTIVE: To evaluate power Doppler ultrasound (PD) as a technique in assessing response to treatment with steroids in rheumatoid hand synovitis. METHODS: Twelve patients with rheumatoid hand synovitis were assessed before and after treatment with steroids. Variables used to assess synovitis activity in each patient included patient visual analog scale (VAS) score for pain, physician assessment score (PAS), erythrocyte sedimentation rate (ESR), and PD of the metacarpophalangeal joints. RESULTS: Nine female and 3 male patients were studied; mean age was 53.3+/-6.5 yrs and mean disease duration 6.5+/-4.5 yrs. All patients had a good clinical response to steroid treatment and there was a significant improvement in the synovitis activity assessments. Wilcoxon signed-rank test using the exact method was applied to the change in disease activity variables. For PD signal, p < 0.002; VAS, p < 0.0016; ESR, p < 0.031; PAS, p < 0.008. CONCLUSION: PD quantifies synovitis and may be a useful adjunct to disease assessment and the response to treatment in RA.

Adult↗
PubMed2001

Persistent radiological changes following miliary tuberculosis in miners exposed to silica dust.

SETTING: Silicosis leads to increased susceptibility to tuberculosis, but it has also been suggested that tuberculosis may interact with intra-pulmonary silica to exacerbate fibrotic lung disease. OBJECTIVES: To investigate the possibility that silicosis developed due to or was exacerbated by tuberculosis. METHODS: In a case series of 15 miners presenting with culture-positive miliary tuberculosis, serial radiographs taken premorbidly, at presentation, and after 2 and 6 months of standard anti-tuberculosis treatment were graded for nodularity using the International Labour Organization system. RESULTS: Increased nodule profusion (compared to premorbid film) remained in 13 (87%) and eight (53%) patients after 2 and 6 months of treatment, respectively, despite clinical improvement in all and documented bacteriological cure in eight (53%). These phenomena, observed irrespective of human immunodeficiency virus (HIV) status, were most pronounced in men with minor premorbid changes. Abnormal pulmonary collagenisation related to silica particles was apparent at post-mortem in two men who died of HIV-associated cryptococcosis after completing TB treatment. CONCLUSIONS: Previous silica exposure appears to result in delayed and potentially incomplete radiological resolution of miliary TB. We postulate that the immune response in tubercles may evoke a 'bystander' fibrotic response, as cytokines play a central role in the pathogenesis of both TB and silicosis.

AIDS-Related Opportunistic Infections↗
PubMed2000

The T9176G mutation of human mtDNA gives a fully assembled but inactive ATP synthase when modeled in Escherichia coli.

A new mutation in human F(1)F(0) ATPase6, T9176G, which changes Leu 217 to an Arg, has been described in two siblings with Leigh syndrome [Carrozzo et al. (2000) Neurology, in press]. This mutation was modeled in Escherichia coli by changing Leu 259 (the equivalent residue) to Arg and the properties of the altered ECF(1)F(0) were compared to those of previously characterized ATPase6 mutants also modeled in the E. coli enzyme. The L259R change produced a fully assembled ECF(1)F(0) which had no significant ATP hydrolysis, ATP synthesis or proton pumping functions. This is very different from previously described human ATPase6 mutations. The presence of Arg at position 259 in subunit a did not make membranes permeable to protons. We conclude that the mutation inhibits functioning by blocking the rotary motor action of the enzyme.

Adenosine Triphosphatases↗
PubMed2000

Sequence and analysis of chromosome 5 of the plant Arabidopsis thaliana.

The genome of the model plant Arabidopsis thaliana has been sequenced by an international collaboration, The Arabidopsis Genome Initiative. Here we report the complete sequence of chromosome 5. This chromosome is 26 megabases long; it is the second largest Arabidopsis chromosome and represents 21% of the sequenced regions of the genome. The sequence of chromosomes 2 and 4 have been reported previously and that of chromosomes 1 and 3, together with an analysis of the complete genome sequence, are reported in this issue. Analysis of the sequence of chromosome 5 yields further insights into centromere structure and the sequence determinants of heterochromatin condensation. The 5,874 genes encoded on chromosome 5 reveal several new functions in plants, and the patterns of gene organization provide insights into the mechanisms and extent of genome evolution in plants.

Animals↗