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Biomedical subjects

R Harling

Publications and source records attributed to R Harling.

16 recordsLinked to original sources
PubMed2004

Burden and cost of imported infections admitted to infectious diseases units in England and Wales in 1998 and 1999.

BACKGROUND: International travel from the UK has been rising, and the number of imported infections has increased. This study aimed to describe the number, nature, origin, clinical burden and cost of imported infections treated in infectious disease units (IDU) in England and Wales. METHOD: Information about all admissions in 1998 and 1999 with illnesses considered to have been acquired during their most recent travel abroad was collected retrospectively by IDUs using a pre-piloted questionnaire. RESULTS AND ANALYSIS: Four of the 23 IDUs in England and Wales were able to complete the questionnaires. They reported a total of 421 travel related admissions during the 2-year period. Three hundred and ninety-two of these cases were attributed to infectious causes, and of these a discharge diagnosis was made for 340 cases. The total number of bed days used to treat cases of imported infection was 2918. The most common diagnosis was malaria. The odds ratio that cases of imported infection were malaria was highest following visits to Africa. The average cost per bed day on the IDUs was around pound sterling 100, and on this basis, the total cost of treating imported infections on the four IDUs in 2 years was around pound sterling 289,000. The relative risk of acquiring an imported infection requiring treatment on an IDU was greatest for travellers to Africa. CONCLUSIONS: From this study, the estimate of the total annual cost of IDU treatment for imported infections in England and Wales is in excess of pound sterling 800,000. Many cases may be preventable with prophylactic medication and vaccination and travel advice on risk reduction. Further information about imported infections would be useful to inform travel medicine services, other clinicians and travellers about the health risks associated with travel to specific areas, and help to target and assess the cost effectiveness of preventative measures.

Adult↗
PubMed2001

Deliberate releases of biological agents: initial lessons for Europe from events in the United States.

The experience of autumn 2001, when anthrax spores were released in the postal system, had considerable consequences in the United States and in Europe. The threat of covert deliberate releases against civilians has become a reality. In Europe, despite the growing number of criminal hoaxes, no cases of anthrax linked to deliberate releases have been reported, and the only contaminated letters were addressed to American embassies abroad. Nevertheless, the time has come for Europe to set up efficient and timely plans to respond to bioterrorism, under the coordination of the European Commission.

Anthrax↗
PubMed2000

PCR-based detection of the polymorphism at codon 136 in the ovine prion protein gene.

In many breeds of sheep, a polymorphism at codon 136 of the prion protein gene has been shown to be strongly associated with the risk of developing scrapie. A single-step procedure for detecting this allelic variation is described here. When performed on a series of animals, the test was in complete agreement with their genotypes as had been previously determined by sequencing. The test is potentially easier and quicker to perform than any of the variety of methods that are currently used for this purpose.

Animals↗
PubMed2000

Survival and epiphytic fitness of a nonpathogenic mutant of Xanthomonas campestris pv. glycines.

Xanthomonas campestris pv. glycines is the causal agent of bacterial pustule disease of soybeans. The objective of this work was to construct a nonpathogenic mutant derived from the pathogenic wild-type strain YR32 and to evaluate its effectiveness in preventing growth of its parent on the soybean phyllosphere. A mini-Tn5-derived transposon was used to generate nonpathogenic mutants. Southern hybridization and pulsed-field gel electrophoresis confirmed the presence of a single transposon in each of the nonpathogenic mutants. One of the nonpathogenic mutants, M715, failed to induce a hypersensitive response in tomato leaves. An ice nucleation gene (inaZ) carried in pJL1703 was introduced into strain YR32 as a reporter gene to demonstrate that the presence of M715 could reduce colonization of the soybean phyllosphere by YR32. de Wit serial replacement analysis showed that M715 competed equally with its wild-type parental strain, YR32. Epiphytic fitness analysis of YR32 in the greenhouse indicated that the population dynamics of strains YR32, YR32(pJL1703), and M715 were similar, although the density of the mutant was slightly less than that of its parent. The M715 mutant was able to survive for 16 days after inoculation on soybean leaves and maintained population densities of approximately 10(4) to 10(5) cells g (fresh weight) of leaf(-1). Therefore, M715 shows promise as an effective biocontrol agent for bacterial pustule disease in soybeans.

Bacterial Outer Membrane Proteins↗
PubMed2000

A prospective, randomised trial of prophylactic antibiotics versus bag extraction in the prophylaxis of wound infection in laparoscopic cholecystectomy.

Septic complications are rare following laparoscopic cholecystectomy if prophylactic antibiotics are given, as demonstrated in previous studies. Antibiotic treatment may be unnecessary and, therefore, undesirable, so we compared two forms of prophylaxis: a cephalosporin antibiotic and bag extraction of the dissected gallbladder. A total of 76 patients undergoing laparoscopic cholecystectomy were randomised to either receive an antibiotic or to have their gallbladder removed from the abdomen in a plastic bag. Complicated cases were excluded. There was a total of 6 wound infections (7.9%), 3 in each of the study groups. All these were associated with skin commensals. There were no other septic complications. Bacteriological studies grouped the organisms isolated from the bile and the wound as potential pathogens and likely commensals. A total of 10 potential pathogens were isolated, 9 of which were found in the group receiving antibiotics. We conclude that septic sequelae of uncomplicated laparoscopic cholecystectomy are uncommon, but clearly not entirely prevented by antibiotic or mechanical prophylaxis. Prophylactic antibiotics may not be required in uncomplicated laparoscopic cholecystectomy. Further study is warranted.

Antibiotic Prophylaxis↗
PubMed1999

Effects of di-isononyl phthalate (DINP) on peroxisomal markers in the marmoset-DINP is not a peroxisome proliferator.

In the present study the systemic toxic potential of di-isononyl phthalate (DINP) was assessed in a 13-week study in marmosets. Particular attention was given to its potential for hepatic peroxisome proliferation. Three groups of four male and four female marmosets received DINP, by oral gavage administration, at dosages of 100, 500 or 2500 mg/kg/day for 13 weeks. A fourth group served as a concurrent Control group and received the vehicle (1% methylcellulose and 0.5% Tween) only. A fifth group received clofibrate at a dosage of 500 mg/kg/day to provide a positive Control for liver peroxisome activity. At the end of the treatment period, the animals were killed and their livers were removed. 3000 x g supernatant and microsomal subcellular fractions were prepared from homogenised liver by differential centrifugation. The peroxisomal marker enzyme activity, cyanide-insensitive palmitoyl CoA oxidase, was assayed in the former, while cytochrome P450 concentration and lauric acid 11- and 12-hydroxylase activities (selective for CYP2E1 and 4A, respectively) were assayed in the microsomes. No statistically significant changes were seen in any of these parameters measured following DINP treatment, compared with the Control. Clofibrate treatment resulted in an approximately 100% increase (p < 0.01) in both male and female marmoset cyanide-insensitive palmitoyl CoA oxidase activity and a similar increase (p < 0.05) in male (only) lauric acid 11-hydroxylase activity. No other changes were statistically significant at the 5% level. These data provide no evidence that DINP was acting as a peroxisome proliferator when administered to marmosets under the conditions of the study.

Animals↗
PubMed1995

Examination of the role of inhibition of cyclic AMP in alpha 2-adrenoceptor mediated contractions of the porcine isolated palmar lateral vein.

1. We have examined the effect of elevation of cellular adenosine 3':5'-cyclic monophosphate (cyclic AMP) on alpha 1- and alpha 2-adrenoceptor-mediated contraction of the isolated palmar lateral vein of the pig. Cellular cyclic AMP was increased by either inhibition of phosphodiesterase by rolipram, or direct activation of adenylyl cyclase by forskolin. 2. Noradrenaline (1 nM-10 microM) caused concentration-dependent contractions of the porcine isolated palmar lateral vein (pD2 7.32 +/- 0.07, n = 10). The selective alpha 1-adrenoceptor antagonist, prazosin (0.1 microM) and the selective alpha 2-adrenoceptor antagonist, rauwolscine (1 microM) caused a 10 fold rightward displacement of the concentration-response curve and a combination of the two antagonists caused a 200 fold rightward displacement of the concentration-response curve. The selective alpha 2-adrenoceptor agonist, UK-14304, also produced concentration-dependent contractions of the palmar lateral vein (pD2 7.70 +/- 0.15, n = 5), but the maximum response was 55.5 +/- 7.6% (n = 5) of that produced by noradrenaline. Prazosin (0.1 microM) failed to affect responses to UK-14304 but rauwolscine, 1 microM, caused a 200 fold rightward displacement. The estimated pKB value for rauwolscine (8.28 +/- 0.19, n = 10) is consistent with inhibition of alpha 2-adrenoceptors. Thus, the porcine isolated palmar lateral vein has a population of alpha 1- and alpha 2-adrenoceptors capable of producing a contraction. 3. Rolipram, 10 micro M, and forskolin, 1 micro M, caused a 2-3 fold rightward displacement of the noradrenaline concentration-response curve (CRC), but 1,9-dideoxyforskolin, 1 micro M, a forskolin analogue which does not activate adenylyl cyclase, failed to produce a significant inhibition of noradrenaline induced contractions. The combination of forskolin (1 micro M) and rolipram (10 micro M) were additive, producing a 20 fold rightward displacement of the noradrenaline CRC.4. Responses to noradrenaline were similarly affected by a combination of rolipram (10 micro M) and prazosin (0.1 micro M) (isolation of alpha 2-adrenoceptors) and the combination of rolipram (10 micro M) and rauwolscine(1 micro M) (isolation of alpha l-adrenoceptors), resulting in a 100 fold rightward displacement of the noradrenaline CRC. Although forskolin inhibited both alpha l- and alpha 2-adrenoceptor-mediated contractions,the effects produced were not similar. In particular, noradrenaline, 0.3-3 micro M, produced a significant contraction in the presence of forskolin (1 micro M) and prazosin (0.1 micro M) (an alpha 2-adrenoceptor-mediated response) but not in the presence of forskolin (1 micro M) and rauwolscine (1 micro M) (an alpha l-adrenoceptor mediated response).5. Five minute exposure to either rolipram (10 micro M) or forskolin (1 micro M) elevated [3H]-cyclic AMP of the porcine isolated palmar lateral vein by approximately 70% and 150-200%, respectively. Neither noradrenaline (1 nM- 100 micro M) nor UK-14304 (1 nM- 100 micro M) affected basal levels of [3H]-cyclic AMP,but both produced a concentration-dependent inhibition of forskolin-stimulated [3H]-cyclic AMP accumulation with a pKi of 7.43 +/- 0.1 (n = 3) and 7.97 +/- 0.18 (n = 3), respectively. The effect of noradrenaline against forskolin-stimulated [3H]-cyclic AMP accumulation was reversed by rauwolscine(1 micro M) but not by prazosin (0.1 micro M). In contrast, alpha 2-adrenoceptor activation did not affect rolipram induced elevation of [3H]-cyclic AMP.6. These findings indicate that M2-adrenoceptor contractions of the porcine isolated palmar lateral vein are not produced by reduction in cellular cyclic AMP per se. It is proposed that this response involves a novel signal transduction mechanism. However, when cellular cyclic AMP has been elevated by agents that stimulate adenylyl cyclase, rather than through inhibition of phosphodiesterase, the ability of alpha 2-adrenoceptors to inhibit cyclic AMP formation may be of functional importance in vascular smooth muscle.

Adrenergic alpha-2 Receptor Agonists↗