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Biomedical subjects

D J Alexander

Publications and source records attributed to D J Alexander.

At least 73 records · Page 4Linked to original sources
PubMed1996

HFA-134a (1,1,1,2-tetrafluoroethane): effects of inhalation exposure upon reproductive performance, development and maturation of rats.

1. HFA-134a was administered to AHA rats by snout-only inhalation for 1 h daily to assess the effects of treatment on reproduction and development. 2. In a fertility study, rats were exposed to atmospheres of 2500, 10,000 or 50,000 p.p.m. HFA-134a throughout gametogenesis, mating, pregnancy and lactation. 3. In a peri- and post-natal study, rats were exposed to HFA-134a from days 17 to 20 of pregnancy and days 1 to 21 post partum to atmospheres of 1800, 9900 or 64,400 p.p.m. 4. The only treatment-related effect was a slight reduction in body weight gain of males of the treated parental generation at 50,000 p.p.m. (fertility study). 5. In neither study were there any adverse effects of HFA-134a on the reproductive performance of treated animals or on the development, maturation or reproductive performance of up to two successive generations.

Animals↗
PubMed1996

Comparison of Newcastle disease viruses isolated from cormorants in Canada and the USA in 1975, 1990 and 1992.

Seventeen Newcastle disease virus (NDV) isolates obtained from cormorants, turkeys, a pelican, and a gull in Canada and the USA collected in 1975, 1990 and 1992 were analyzed for relatedness by monoclonal antibody profiling. In addition, nucleotide sequence analysis was performed in two areas of the fusion (F) gene for 5 of the isolates. No difference in the antigenicity of these 17 viruses, as determined by monoclonal antibody binding patterns, was seen. The amino acid sequences obtained via nucleotide sequencing at the cleavage site of the F protein showed that all the isolates tested had two pairs of basic amino acids immediately upstream of the cleavage site, and a phenylalanine residue at the N-terminus of the F1 protein, which is consistent with velogenic NDV. The deduced amino acid sequence obtained at the cleavage site of the F protein from 6 of the isolates was virtually identical regardless of the species, year of isolation, or location. However, the 1975 cormorant isolate showed marked differences from the 1990-1992 isolates in the nucleotide and deduced amino acid sequence of the F gene signal region. These data indicate that the 1990 and 1992 outbreaks were caused by the same epizootic virus and further suggest that the population of NDV in these wild birds may be very stable. The belief that the velogenic NDV circulating in cormorants in 1992 was transmitted into the free-ranging turkey flocks located near the cormorants in North Dakota is supported by the present study in which no distinction could be made between the viruses isolated from turkeys or wild birds.

Amino Acid Sequence↗
PubMed1996

Randomized trial of periportal peritoneal bupivacaine for pain relief after laparoscopic cholecystectomy.

The aim of this study was to determine whether injection of a long-acting local anaesthetic, in relation to the port sites at the level of the parietal peritoneum, would reduce postoperative pain following laparoscopic cholecystectomy. Patients were entered into a randomized, prospective, double-blind study comparing the effects of a standard technique, in which bupivacaine (total of 20 ml, 0.5 per cent) was injected into the subcutaneous periportal tissue around the four port sites, and a technique in which bupivacaine (total of 20 ml, 0.25 per cent) was injected into the subcutaneous periportal tissue as above with the addition of periportal parietal peritoneal injection of bupivacaine (total of 20 ml, 0.25 per cent). Two scores for pain, with the patient at rest, and on movement, were assessed 6 and 18 h after surgery using a visual analogue pain scale. Median pain score was significantly higher in patients who received standard technique (n = 40) than in those given peritoneal injection (n = 40) at both 6 (rest = 3.0 versus 1.0, movement = 5.0 versus 2.9) and 18 h (rest = 1.9 versus 0, movement = 3.2 versus 1.2). Both opiate and oral analgesic requirements were reduced in patients administered peritoneal injection, although this was not statistically significant. The addition of periportal injection of bupivacaine at the level of the parietal peritoneum, performed under direct vision, reduces pain after laparoscopic cholecystectomy.

Adult↗
PubMed1995

Combination therapy using adrenaline and heater probe to reduce rebleeding in patients with peptic ulcer haemorrhage: a prospective randomized trial.

A prospective randomized trial was performed to assess the efficacy of the combined therapy of endoscopic injection of adrenaline and heater probe application in the management of patients with major peptic ulcer haemorrhage. Some 153 consecutive patients were randomized to receive either local injection of adrenaline (1:10,000) followed by heater probe thermocoagulation (74 patients) or no endoscopic treatment (79 patients). The two groups were well matched with regard to age, haemoglobin concentration on admission, non-steroidal anti-inflammatory drug usage and endoscopic findings. More patients in the treatment group were in shock on admission (21 versus 13). Initial haemostasis was achieved in all patients randomized to endoscopic therapy. Rebleeding occurred in fewer treated than control patients (five versus 16, P = 0.01). The treated group also had fewer deaths (zero versus two) and requirement for operation (two versus six). The results show that the combination of sclerotherapy with adrenaline and subsequent thermocoagulation reduces the rate of rebleeding in peptic ulcer haemorrhage.

Adult↗
PubMed1995

Serological studies of influenza viruses in pigs in Great Britain 1991-2.

Samples from a sow serum bank representative of the pig population of Great Britain collected during 1991-2, were examined for antibodies to influenza A, B and C viruses, using viruses which had been isolated from a variety of hosts. For influenza A viruses there was evidence of the continued circulation of classical swine H1N1 virus (26%) seroprevalence), and human H3N2 viruses (39%) which are antigenically most closely-related to A/Port Chalmers/1/73 virus. In addition antibodies were detected to A/swine/England/201635/92 (8%), a strain of H3N2 virus which appears to have arisen by antigenic drift from conventional H3N2 swine strains. Specific antibodies (2%) were detected to an H1N1 virus (A/swine/England/195852/92) related most closely to avian H1N1 strains. In tests with human H1N1 and H3N2 viruses, excluding isolates from pigs, the highest seroprevalence was detected to the prevailing strains from the human population. Serological tests with avian H4 and H10, human H2, equine 1 and 2 influenza A viruses were all negative. Seven pigs seropositive by haemagglutination-inhibition, virus neutralization and immunoblotting assays for antibody to influenza B virus, were randomly distributed geographically suggesting that influenza B viruses may be transmitted to pigs but fail to spread. The seroprevalence to influenza C viruses was 9.9% indicating that these viruses are widespread in pigs. These results provide further evidence that the pig can be infected by a number of influenza viruses, some of which may have significance in the epidemiology of human influenza.

Animals↗
PubMed1995

Safety of propellants.

Chlorofluorocarbon (CFC) propellants used in metered dose inhalers (MDI) must be replaced under the terms of the Montreal Protocol. Following a review of the available data, HFA134a (1,1,1,2 tetrafluoroethane) was selected as a potential alternative propellant. However, because this data was insufficient to satisfy the stringent requirements for pharmaceuticals, additional toxicological assessments were performed. These included genotoxicology, animal inhalation studies, reproductive toxicology, local tolerability and safety pharmacology studies. A special grade of HFA134a, containing relatively high concentrations of all likely impurities, was used for all pivotal studies. HFA134a was devoid of genotoxicity and had exceptional low acute toxicity. No toxicity was seen in rats or dogs exposed to concentrations of up to 5% or 12% respectively for up to one year. No fetotoxicity, effects on reproductive performance, peri- or postnatal development was demonstrated. HFA134a was devoid of oncogenic potential in rats and mice. There was no evidence of sensitisation or local irritation to the skin or eyes. All species demonstrated high systemic HFA134a concentrations. An extensive toxicological evaluation, at very high multiples of the likely patient exposure, has indicated that HFA134a is a suitable alternative to CFC propellants for MDIs.

Aerosol Propellants↗
PubMed1995

HFA-134a (1,1,1,2-tetrafluoroethane); lack of oncogenicity in rodents after inhalation.

1. Groups of 60 male and 60 female B6C3F1 mice or HanIbm Wistar rats were exposed to HFA-134a using snout-only inhalation exposure techniques for periods of one hour daily for at least 104 weeks. HFA-134a was delivered directly from cylinders at vapour concentrations of 2500, 15,000 and 75,000ppm for mice and from metered-dose inhalers at vapour concentrations of 2500, 10,000 and 50,000ppm for rats. 2. Intended dosages were achieved. 3. Evidence of absorption was found at each dose level and was dose related. 4. Neither species suffered treatment related effects on survival, clinical signs, body weights, haematology nor on the type, incidence, site or severity of gross lesions. 5. There was no effect of treatment on the type, incidence, site or severity of neoplasms in mice or rats. 6. There were no non-neoplastic findings related to treatment in mice. 7. HFA-134a was considered not to be oncogenic and to provide a safe alternative to chlorofluorocarbons for use in pharmaceutical metered-dose inhalers.

Absorption↗
PubMed1995

An overview of the toxicology of HFA-134a (1,1,1,2-tetrafluoroethane).

1. This paper reviews the results of preclinical toxicology studies on HFA-134a carried out by Glaxo Research and Development Ltd. 2. A comprehensive range of studies was conducted in animal models suitable for the type of investigation. 3. The inhalation route of administration was used in all in vivo studies (with the exception of local tolerance and sensitisation studies) as patients will be exposed only to vapour during actuation of metered-dose inhalers. Cell cultures used for in vitro studies were also exposed to the vapour. 4. There was no mortality of rodents or dogs at extremely high vapour concentrations (81%v/v) 5. HFA-134a was considered not to be toxic or oncogenic and to provide a safe alternative to chlorofluorocarbons for use in pharmaceutical metered-dose inhalers.

Administration, Inhalation↗
PubMed1995

Cleavability of hemagglutinin from an extremely virulent strain of avian influenza virus containing a unique cleavage site sequence.

An avian influenza virus, A/turkey/England/50-92/91 (H5N1), showed extremely high virulence in chickens, although its hemagglutinin (HA) cleavage site sequence (R-K-R-K-T-R), having a nonbasic (Thr) residue at the second position (P-2) from the carboxyl terminus of HA1, does not conform to the previously established consensus sequence motif, X-X-R/K-X-R/K-R (X = nonbasic residue), for highly virulent phenotype of the H5 virus. When we evaluated the HA cleavability of this strain in chicken embryo fibroblast culture, we observed that, unlike other HAs with a Thr residue at P-2, this HA was efficiently cleaved. These findings suggest that a nonbasic residue at the P-2 does not affect its recognition and catalyzation by cleavage enzymes that are otherwise influenced by steric structure around the cleavage site.

Amino Acid Sequence↗
PubMed1994

Right atrial electrocardiography: a technique for the placement of central venous catheters for chemotherapy or intravenous nutrition.

Central venous catheters used for chemotherapy are usually sited so that the catheter tip lies in the superior vena cava. This study evaluated right atrial electrocardiography as a method of accurately placing the catheter tip in 34 patients over a period of 22 months. An electrocardiograph adaptor was connected to the catheter and the tip advanced into a central vein until a biphasic P wave was identified. In 31 of 34 patients the characteristic P wave changes were observed and the position of the catheter tip confirmed by screening to be in the superior vena cava. Right atrial electrocardiography is an accurate, reliable and rapid method of positioning the tip of a central venous catheter, and avoids or reduces exposure to radiation.

Catheterization, Central Venous↗
PubMed1994

Evaluation of the molecular basis of pathogenicity of the variant Newcastle disease viruses termed "pigeon PMV-1 viruses".

The amino acid sequence at the F2/F1 cleavage site was determined for 15 strains of the so-called pigeon PMV-1 (PPMV-1) variant of Newcastle disease virus (NDV) which showed close antigenic identity, determined by their reactions with a panel of 28 monoclonal antibodies, but considerable variation in their pathogenicity for chickens. Thirteen of the isolates possessed the motif 112G-R-Q-K-R-F117. This motif was seen for one virus which had initially low pathogenicity and remained unaltered when virulence of the virus for chickens was increased by bird to bird passage. The two other viruses had the sequence 112R-R-Q-K-R-F117 at the cleavage site which is more typical of virulent viruses, however, pathogenicity index tests indicated that these isolates were of moderate and low pathogenicity. The nucleotide sequence coding for the HN/HN0 extension region was determined for two of the PPMV-1 isolates. In both cases a stop codon was present indicating that the product for these viruses would be HN571. We conclude that the wide variation in pathogenicity of the variant PPMV-1 for chickens is not related to variation in the amino acid motif at the F2/F1 cleavage site nor due to production of HN0 which may also influence pathogenicity. The high virulence of some of the viruses examined confirms that a double pair of basic amino acids in the region of the F2/F1 cleavage site is not necessary for the full expression of virulence.

Amino Acid Sequence↗
PubMed1994

Deduced amino acid sequences of the haemagglutinin of H5N1 avian influenza virus isolates from an outbreak in turkeys in Norfolk, England.

The deduced amino acid sequences of the haemagglutinins of avian influenza viruses, isolated from an outbreak in turkeys in Norfolk, England in 1991/92, were determined by PCR amplification and cycle sequencing. Both the highly pathogenic and avirulent isolates had the same cleavage site sequence with multiple-basic amino acids, which normally would be expected only for the former. Clones derived by plaque picking from the highly pathogenic isolate ranged from low to very high pathogenicity in vivo and these, and the original isolates, showed nucleotide and amino acid variation at one or more of five possible sites, none of which were at the cleavage site. None of these site variations correlated with pathogenicity, suggesting that the factor responsible for the suppression of the expected effects of the multiple-basic amino acid haemagglutinin cleavage site in the avirulent isolate may not have been part of the haemagglutinin amino acid sequence.

Amino Acid Sequence↗
PubMed1994

Isolation of an influenza A virus of unusual subtype (H1N7) from pigs in England, and the subsequent experimental transmission from pig to pig.

A novel H1N7 influenza virus (A/swine/Eng/191973/92) was isolated from nasal swabs collected from two pigs on a farm where there had been recent clinical disease due to infection with an H1N1 virus (A/swine/Eng/195852/92). Antigenically, the haemagglutinin (HA) of the H1N7 virus was related most closely to the HA of A/USSR/90/77, whilst the neuraminidase (NA) appeared to be related most closely to the NA of A/equine/Prague/1/56 (H7N7). Pigs infected experimentally with A/swine/Eng/191973/92 developed mild clinical signs, excreted virus into the nasal passages for up to nine days after infection, appeared normal at necropsy, transmitted the virus to sentinel pigs, but seven out of eight pigs failed to seroconvert. These findings suggest that the H1N7 virus has a low pathogenicity for pigs, resulting in limited virus multiplication which is insufficient to stimulate a detectable primary humoral immune response.

Animals↗
PubMed1993

Pathogenicity of a swine influenza H1N1 virus antigenically distinguishable from classical and European strains.

An H1N1 strain of influenza virus (A/swine/England/195852/92) isolated recently from clinical epizootics in pigs was transmitted experimentally to six-week-old specific pathogen-free pigs. Between one and four days after inoculation the infected pigs developed pyrexia and showed signs of coughing, sneezing and anorexia. Seroconversion was detected seven days after infection. Virus was isolated from nasal swabs and tissues up to four days after infection, but was not recovered from faeces. Virus was isolated from serum samples taken from each infected animal for a period of only one day between one and three days after infection. The pathology was characterised by a widespread interstitial pneumonia for up to 21 days after infection, lesions in the bronchi and bronchioles for up to seven days after infection, and haemorrhagic lymph nodes. Epithelial damage in the bronchial generations as a result of the virus infection was demonstrated by immunocytochemistry and electron microscopy.

Animals↗