Search PubMed⌕ Search

Biomedical subjects

D J Alexander

Publications and source records attributed to D J Alexander.

At least 19 recordsLinked to original sources
PubMed2006

Recent epidemiology and ecology of influenza A viruses in avian species in Europe and the Middle East.

There have been at least ten distinct outbreaks of LPAI or HPAI in poultry caused by H5 or H7 viruses in the last eight years in Europe and the Middle East. There appears to be an increased occurrence of such episodes consistent with global trends. As a result, surveillance systems have been enhanced to facilitate early detection of infection in poultry, together with active surveillance of wild bird populations. These complementary activities have resulted in the detection of a number of viruses in wild bird populations, including some with high genetic similarity to newly detected viruses in poultry, for example, H7N3 in Italy and H7N7 in the Netherlands. Furthermore, there is evidence for continued circulation of H5 and H7 viruses in wild Anseriformes, thereby presenting a real and current threat for the introduction of viruses to domestic poultry, especially those reared in outdoor production systems. Viruses of H9N2 subtype continue to circulate widely in the Middle East and are associated with significant disease problems in poultry. The epidemiology has the potential to be complicated further by introduction of novel viruses through illegal importation of captive birds, such as was detected with H5N1 in Belgium in 2004. Continual genetic exchange in the avian virus gene pool and independent evolution of all gene segments either within an individual host species or among wild bird hosts suggests that these viruses are not in evolutionary stasis in the natural reservoir.

Animals↗
PubMed2006

Avian influenza viruses and human health.

Influenza A viruses cause natural infections of humans, some other mammals and birds. Few of the 16 haemagglutinin and nine neuraminidase subtype combinations have been isolated from mammals, but all subtypes have been isolated from birds. In the 20th century, there were four pandemics of influenza as a result of the emergence of antigenically different strains in humans: 1918 (H1N1), 1957 (H2N2), 1968 (H3N2) and 1977 (H1N1). Influenza A viruses contain eight distinct RNA genes and reassortment of these can occur in mixed infections with different viruses. The 1957 and 1968 pandemic viruses differed from the preceding viruses in humans by the substitution of genes that came from avian viruses, suggesting they arose by genetic reassortment of viruses of human and avian origin. Up to 1995, there had been only three reports of avian influenza viruses infecting humans, in 1959, 1977 and 1981 (all H7N7), but, since 1996, there have been regular reports of natural infections of humans with avian influenza viruses: in England in 1996 (H7N7), Hong Kong 1997 (H5N1), 1999 (H9N2), and 2003 (H5N1), in The Netherlands 2003 (H7N7), Canada 2004 (H7N3), Vietnam 2004 (H5N1) and Thailand 2004 (H5N1). The H5N1 virus is alarming because 51 (64 %) of the 80 people confirmed as infected since 1997 have died.

Animals↗
PubMed2005

Induction of heat shock protein 70 in rat olfactory epithelium by toxic chemicals: in vitro and in vivo studies.

We have previously developed a rat nasal explant system for investigating upper respiratory tract toxicity, and the aims of this study were to determine whether heat shock protein (HSP) 70 is induced in this model following exposure to carbon tetrachloride (CCl4), dimethyl adipate (DMA), methyl iodide (CH3I) or paracetamol, and whether HSP70 can also be induced in the nasal cavity in vivo. Intracellular ATP was significantly depleted in ethmoturbinates incubated for 4 h with the toxins (0-100 mM; EC50 concentrations: CCl4 32 mM, DMA 3 mM, CH3I 1.5 mM, paracetamol 70 mM), but there was little induction of HSP70. Turbinates were then incubated for 1 h with CCl4 (5 mM), DMA (1.5 mM), CH3I (0.57 mM) or paracetamol (30 mM) and allowed to recover for up to 24 h. Treatment with CCl4, DMA or paracetamol resulted in 250-300% induction of HSP70. Male rats were administered a single oral dose of CCl4 (1600 mg/kg) and killed 16 h later. Degenerative lesions (epithelial undulation and hydropic vacuolation) were evident in the olfactory epithelium, and immunohistochemical analysis of HSP70 revealed increased staining in, or proximate to, areas of damage. Thus, HSP70 can be induced in the olfactory epithelium both in vitro and in vivo.

Acetaminophen↗
PubMed2004

Strains of avian paramyxovirus type 1 of low pathogenicity for chickens isolated from poultry and wild birds in Denmark.

Twenty-one strains of avian paramyxovirus type 1 of low virulence for chickens were isolated in Denmark between 1996 and the beginning of 2003. The low virulence of the strains was demonstrated by sequencing the fusion (F) gene at the cleavage site motif and in some cases by determining the intracerebral pathogenicity index in day-old chicks. By using a panel of monoclonal antibodies it was shown that the isolates belonged to four different antigenic groups (five C2 isolates, six E isolates, six H isolates and four G/Q isolates). They were placed in three distinguishable genetic groups by phylogenetic analysis of a partial sequence of the F gene. The origin of the six E isolates was probably contaminated vaccines; the other viruses were isolated from wild birds and from poultry which probably came into contact with wild birds.

Animals↗
PubMed2004

Foetal rat lung epithelial (FRLE) cells: alterations in cellular homeostasis and gene expression in response to etoposide, hydrogen peroxide and sodium butyrate.

Genomics technology offers a way of detecting the effects of a toxin on the expression of many genes in a single experiment. We have previously partially characterised a foetal rat lung epithelial (FRLE) cell line and shown that it is suitable for use in a pneumocytotoxicity screen. In this study, we wanted to ascertain whether we could use alterations in FRLE cell gene expression as a sensitive marker of cell stress. Sodium butyrate and etoposide were shown to arrest FRLE cell cycle at G0/G1 and G2/M phase of the cell cycle, respectively and this was associated with a decrease in the number of cells in culture. Following 24 h of culture both compounds caused a statistically significant increase in the mRNA levels of the cell cycle inhibitory protein, gadd153, whereas p21 was statistically altered by etoposide only. Hydrogen peroxide induced growth arrest at low concentrations (< or =250 microM) following 24 h of culture. We could not detect an increase in apoptosis or in the mRNA levels of the pro-apoptotic protein bax in FRLE cells following culture with hydrogen peroxide or etoposide. Thus, it was possible to correlate cellular perturbations in FRLE cells with alterations in gene expression, demonstrating that these cells are suitable for use in a toxicity screen.

Animals↗
PubMed2004

Foetal rat lung epithelial (FRLE) cells: partial characterisation and response to pneumotoxins.

Cultured cell lines are routinely used for in vitro toxicity screens, reducing the requirement for animal studies during the development of new pharmaceutical, agrochemical and cosmetic products. The foetal rat lung epithelial (FRLE) cell line was originally derived from alveolar type II cells (ATII) of the lung. The aims of this study were to further characterise FRLE cells and investigate their potential for screening for pneumotoxins. The cells were found to have retained some of the features of their progenitor cells, namely the expression of cytokeratin proteins, specifically cytokeratin 18, and the ability to actively accumulate the non-selective contact herbicide paraquat. However, the cells have lost the ability to synthesise surfactant protein mRNA and no longer contain multiple lamellar bodies. Toxins that damage ATII cells in vivo (cadmium chloride, cobalt chloride and paraquat) were found to induce cytotoxicity in FRLE cells, as did the non-specific pneumotoxin nitrofurantoin, and hydrogen peroxide. However, the cells were less sensitive to the effects of compounds that require metabolic activation (1-nitronaphthalene, coumarin and butylated hydroxytoluene) and the hepatotoxin bromobenzene. Thus, FRLE cells appear to be a good in vitro model for monitoring the potential toxicity to ATII cells and could be used as an initial screen for pneumotoxicity.

Animals↗
PubMed2004

A molecular epidemiological investigation of isolates of the variant avian paramyxovirus type 1 virus (PPMV-1) responsible for the 1978 to present panzootic in pigeons.

A sequence of 375 nucleotides, which included the region encoding the cleavage activation site and signal peptide of the fusion protein gene, was determined for 178 isolates of the pigeon variant strain of Newcastle disease virus (PPMV-1). These were compared with the sequences of 47 similar isolates published by GenBank, which included 30 isolates from pigeons and 17 representatives from each sublineage of avian paramyxovirus type 1. The resulting alignment was analysed phylogenetically using maximum likelihood and the results are presented as unrooted phylogenetic trees. By phylogenetic analysis all the PPMV-1 isolates except one were placed in lineage 4b (VIb). Within this lineage there was considerable genetic heterogeneity, which appears to be predominantly influenced by the date of isolation and, to a lesser extent, geographical origins of the isolates. There were two large distinguishable groups, 4bi and 4bii. The earliest isolate available, PIQPI78442, isolated in 1978 in Iraq, was situated at the node from which the two groups diverge.

Animals↗
PubMed2004

Patients awaiting laparoscopic cholecystectomy--can preoperative complications be predicted?

AIMS: To determine the nature and incidence of gallstone-related complications arising in patients awaiting laparoscopic cholecystectomy and to formulate a strategy to detect those most in need of urgent intervention. PATIENTS AND METHODS: A retrospective analysis of the case notes of 337 consecutive patients undergoing laparoscopic cholecystectomy under a single surgeon in a district general hospital between 1995 and 1999. RESULTS: Of patients awaiting laparoscopic cholecystectomy, 65 (19.3%) were documented as suffering significant on-going symptoms, of whom 19 (5.6%) required hospital admission or urgent surgical review at median 8.9 weeks (range 0.1-32.3 weeks) after being placed on the waiting list. Factors predictive of symptom recurrence included: (i) initial acute presentation; (ii) diagnoses of jaundice, pancreatitis, or acute cholecystitis; (iii) elevation of amylase or liver function tests; and (iv) small stones on ultrasonography examination. CONCLUSIONS: A significant proportion of patients awaiting laparoscopic cholecystectomy experience stone-related complications requiring hospital admission. We feel it is possible to reduce this number by selecting those most at risk on the basis of their history and pre-operative investigations for more urgent intervention.

Adult↗
PubMed2003

Human health implications of avian influenza viruses and paramyxoviruses.

Among avian influenza viruses and avian paramyxoviruses are the aetiological agents of two of the most devastating diseases of the animal kingdom: (i). the highly pathogenic form of avian influenza, caused by some viruses of the H5 and H7 subtypes, and (ii). Newcastle disease, caused by virulent strains of APMV type 1. Mortality rates due to these agents can exceed 50% in naïve bird populations, and, for some strains of AI, nearly 100%. These viruses may also be responsible for clinical conditions in humans. The virus responsible for Newcastle disease has been known to cause conjunctivitis in humans since the 1940s. The conjunctivitis is self-limiting and does not have any permanent consequences. Until 1997, reports of human infection with avian influenza viruses were sporadic and frequently associated with conjunctivitis. Recently, however, avian influenza virus infections have been associated with fatalities in human beings. These casualties have highlighted the potential risk that this type of infection poses to public health. In particular, the pathogenetic mechanisms of highly pathogenic avian influenza viruses in birds and the possibility of reassortment between avian and human viruses in the human host represent serious threats to human health. For this reason, any suspected case should be investigated thoroughly.

Animals↗
PubMed2003

Rapid in vitro assessment of the virulence of Newcastle disease virus isolates using the ligase chain reaction.

The ligase chain reaction was used to assess the virulence of isolates of Newcastle disease virus. In the main study, 18/18 virulent isolates whose nucleotide sequences that code for the cleavage site and fusor peptide regions were known, successfully ligated oligonucleotides in a primer mix for virulent viruses termed VPM. Five of these isolates yielded a more intense ligated product with a second primer mix for virulent viruses called VPM1. No ligation was evident with eight avirulent isolates in tests with VPM or VPM1, however, each of these viruses did yield a strong ligated product with the primer mix for avirulent viruses (AVPM) as did one virulent isolate considered to be a mixture. Two virulent Australian isolates, 1238/1998 and 1248/1998, showed low but seemingly specific ligation with AVPM. In a blind study, 8/9 virulent isolates whose sequences were unknown ligated primers in VPM. Three avirulent and one virulent isolate, the latter again probably a mixture, ligated primers in AVPM. Ligation of oligonucleotides in VPM and AVPM was detectable in mixtures where virulent and avirulent isolates represented 0.1% and 0.01% by volume respectively of the viral population. The results indicate that LCR offers a potential in vitro alternative to current in vivo tests for virulence determination of Newcastle disease virus isolates.

Ligase Chain Reaction↗
PubMed2003

A molecular epidemiological study of avian paramyxovirus type 1 (Newcastle disease virus) isolates by phylogenetic analysis of a partial nucleotide sequence of the fusion protein gene.

A sequence 375 nucleotides in length, which included the region encoding the cleavage activation site and signal peptide of the fusion protein gene, was determined for 174 isolates of Newcastle disease virus (avian paramyxovirus type 1). These were compared with the sequences of 164 isolates published on GenBank, and the resulting alignment was analysed phylogenetically using maximum likelihood. The results are presented as unrooted phylogenetic trees. Briefly, the isolates divided into six broadly distinct groups (lineages 1 to 6). Lineages 3 and 4 were further subdivided into four sublineages (a to d) and lineage 5 into five lineages (a to e). Considerable genetic heterogeneity was detected within avian paramyxoviruses type 1, which appears to be influenced by host, time and geographical origin. It is concluded that by using this dataset it will be possible to type future virus isolates rapidly on the basis of their nucleotide sequence and make inferences about their origins.

Animals↗
PubMed2003

Report on avian influenza in the Eastern Hemisphere during 1997-2002.

Since the Fourth International Symposium on Avian Influenza (AI) there has been considerable AI activity in the Eastern Hemisphere. The higher profile of AI resulting from the human infections with H5N1 and H9N2 viruses in Hong Kong, in 1997 and 1999, respectively, resulted in increased reporting and active surveillance. There have been three reported incidents of high-pathogenicity (HP) AI: H5N2 in northeastern Italy in 1997 (eight outbreaks); H5N1 in Hong Kong in 1997 recurring in 2001 and 2002; H7N1 in northeasten Italy resulting in 413 outbreaks in 1999-00. The Italian HPAI outbreaks were preceded by 199 H7N1 low-pathogenicity (LP) AI outbreaks in 1999, and this virus continued to cause some problems after the eradication of HPAI. During the second half of the 1990s outbreaks of LPAI due to H9N2 subtype have been reported in Germany, Italy, Ireland, South Africa, Hungary, Korea, China, Hong Kong, countries of the Middle East, Iran, and Pakistan. The continued presence of virus of this subtype in the Middle and Far East may mean it is becoming an established endemic disease in those regions. Other more restricted outbreaks in poultry have resulted in the isolation of LPAI viruses of H5, H6, H7, and H10 subtypes.

Animals↗
PubMed2003

Should we change the definition of avian influenza for eradication purposes?

The current definitions of high-pathogenicity avian influenza (HPAI), formulated over 10 years ago, were aimed at including viruses that were overtly virulent in in vivo tests and those that had the potential to become virulent. At that time the only virus known to have mutated to virulence was the one responsible for the 1983-84 Pennsylvania epizootic. The mechanism involved has not been seen in other viruses, but the definition set a precedent for statutory control of potentially pathogenic as well as overtly virulent viruses. The accumulating evidence is that HPAI viruses arise from low-pathogenicity avian influenza (LPAI) H5 or H7 viruses infecting chickens and turkeys after spread from free-living birds. At present it can only be assumed that all H5 and H7 viruses have this potential and mutation to virulence is a random event. Therefore, the longer the presence and greater the spread in poultry the more likely it is that HPAI virus will emerge. The outbreaks in Pennsylvania, Mexico, and Italy are demonstrations of the consequences of failing to control the spread of LPAI viruses of H5 and H7 subtypes. It therefore seems desirable to control LPAI viruses of H5 and H7 subtype in poultry to limit the probability of a mutation to HPAI occurring. This in turn may require redefining statutory AI. There appear to be three options: 1) retain the current definition with a recommendation that countries impose restrictions to limit the spread of LPAI of H5 and H7 subtypes; 2) define statutory AI as an infection of birds/poultry with any AI virus of H5 or H7 subtype; 3) define statutory AI as any infection with AI virus of H5 or H7 subtype, but modify the control measures imposed for different categories of virus and/or different types of host.

Animals↗
PubMed2002

Avian paramyxoviruses and influenza viruses isolated from mallard ducks (Anas platyrhynchos) in New Zealand.

A comprehensive study using virological and serological approaches was carried out to determine the status of live healthy mallard ducks (Anas platyrhynchos) in New Zealand for infections with avian paramyxoviruses (APMV) and influenza viruses (AIV). Thirty-three viruses isolated from 321 tracheal and cloacal swabs were characterized as: 6 AIV (two H5N2 and four H4N6), 10 APMV-1 and 17 APMV-4. Of 335 sera samples tested for AIV antibodies, 109 (32.5%) sera were positive by nucleoprotein-blocking ELISA (NP-B-ELISA). Serum samples (315) were examined for antibody to APMV-1, -2, -3, -4, -6, -7, -8, -9 by the haemagglutination inhibition test. The largest number of reactions, with titres up to > or =1/64, was to APMV-1 (93.1%), followed by APMV-6 (85.1%), APMV-8 (56%), APMV-4 (51.7%), APMV-7 (47%), APMV-9 (15.9%), APMV-2 (13.3%) and APMV-3 (6.0%). All of the H5N2 isolates of AIV and the APMV-1 isolates from this and earlier New Zealand studies had low pathogenicity indices assessed by the Intravenous Pathogenicity Index (IVPI) with the result 0.00 and Intracerebral Pathogenicity Index (ICPI) with results 0.00-0.16. Partial genomic and antigenic analyses were also consistent with the isolates being non-pathogenic. Phylogenetic analysis of the 10 APMV-1 isolates showed 9 to be most similar to the reference APMV-1 strain D26/76 originally isolated in Japan and also to the Que/66 strain, which was isolated in Australia. The other isolate was very similar to a virus (MC 110/77) obtained from a shelduck in France.

Animals↗
PubMed2002

Rapid pathotyping of Newcastle disease virus using a single-chain Fv displayed on phage against the C-terminal end of the F2 polypeptide.

Filamentous bacteriophage display technology has been used to generate specific antibody fragments for differentiating virulent and avirulent Newcastle disease virus. A single-chain Fv fragment to the motif (112)RRQ(114), present at the F2 C-terminal end of many virulent Newcastle disease virus isolates, was isolated from a phage display library derived from a rabbit immunized with a peptide conjugate. An ELISA evaluation was carried out to test its ability to differentiate between 11 avirulent and 34 virulent NDV isolates. The antibody fragment reacted with 25/28 virulent viruses with the putative motif (112)RRQ(114). The three exceptions were viruses with an arginine instead of glycine, at position 110 of the fusion protein, just preceding the cleavage site. Five of six virulent isolates, whose predicted motif was different from that usually found in virulent strains, also tested negative. However, the antibody did react with one isolate with the motif (112)KRQ(114). There was no apparent reactivity with any of the avirulent isolates tested. We conclude that this antibody may, in the future, be a useful aid for the pathotyping of NDV isolates.

Amino Acid Motifs↗
PubMed2002

Pancreatic debridement in a district general hospital--viable or vulnerable?

Little is known about the outcome after pancreatic debridement in the district general hospital (DGH) setting and the debate about centralisation of pancreatic surgical services continues. We retrospectively reviewed our experience over 2 years, looking particularly at mortality, morbidity and cost. Of 12 cases treated during this period, 8 were women and 7 were gallstone induced. The mean pre-operative age was 56.5 years and pre-operative Apache II score was 15. The rates for postoperative morbidity and mortality were 67% and 25%, respectively In half, digital necrosectomy was performed and in half a regional pancreatic resection. These figures are similar to others found in the literature (comparison with 15 contemporary series). The median cost per patient was 21,487 pounds, mainly due to ITU accommodation (57.4% of total costs). This is similar to other previously published rates and the rate from our local tertiary centre. It is concluded that acceptable results for pancreatic debridement are producible in the DGH at economically viable levels.

Adult↗
PubMed2001

Laparoscopic cholecystectomy without routine operative cholangiography does not result in significant problems related to retained stones.

BACKGROUND: This study investigated whether failure to identify common bile duct stones at laparoscopic cholecystectomy results in significant postoperative complications related to retained stones. METHODS: We performed a retrospective analysis of the case notes of 377 consecutive patients undergoing laparoscopic cholecystectomy without routine operative cholangiography under a single surgeon in a district general hospital between 1995 and 1999. Highly selective preoperative endoscopic retrograde cholangiopancreatography (ERCP) was employed to identify and manage suspected bile duct stones in pancreatitis, jaundice, persistently elevated liver function tests, or a dilated common bile duct. RESULTS: Eighteen (4.8%) of 377 patients presented postoperatively with symptoms/signs suggesting biliary pathology. Two (0.5%) were confirmed to have retained duct stones/debris (ultrasound/ERCP); both recovered with conservative treatment. Only 1 patient of 274 (0.4%) without preoperative ERCP subsequently presented with a symptomatic retained stone, the other having been stented preoperatively. CONCLUSIONS: Highly selective preoperative ERCP without routine operative cholangiography is not associated with a significant increase in morbidity/mortality related to retained stones following laparoscopic cholecystectomy.

Adolescent↗