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Biomedical subjects

A Egan

Publications and source records attributed to A Egan.

At least 19 recordsLinked to original sources

Construct validity for the LAPSIM laparoscopic surgical simulator.

BACKGROUND: The skills required for laparoscopic surgery are amenable to simulator-based training. Several computerized devices are now available. We hypothesized that the LAPSIM simulator can be shown to distinguish novice from experienced laparoscopic surgeons, thus establishing construct validity. METHODS: We tested residents of all levels and attending laparoscopic surgeons. The subjects were tested on eight software modules. Pass/fail (P/F), time (T), maximum level achieved (MLA), tissue damage (TD), motion, and error scores were compared using the t-test and analysis of variance. RESULTS: A total of 54 subjects were tested. The most significant difference was found when we compared the most (seven attending surgeons) and least experienced (10 interns) subjects. Grasping showed significance at P/F and MLA (p < 0.03). Clip applying was significant for P/F, MLA, motion, and errors (p < 0.02). Laparoscopic suturing was significant for P/F, MLA, T, TD, as was knot error (p < 0.05). This finding held for novice, intermediate, and expert subjects (p < 0.05) and for suturing time between attending surgeons and residents (postgraduate year [PGY] 1-4) (p < 0.05). CONCLUSIONS: LAPSIM has construct validity to distinguish between expert and novice laparoscopists. Suture simulation can be used to discriminate between individuals at different levels of residency and expert surgeons.

Clinical Competence↗

Abattoir-associated Q fever: a Q fever outbreak during a Q fever vaccination program.

OBJECTIVES: To investigate an abattoir outbreak of Q fever in southem New South Wales with reference to the protective effect and safety of the formalin-inactivated Q fever vaccine (Q Vax) administered before and during the outbreak. METHODS: In September 1998, after notification of four Q fever cases in the abattoir, a cohort investigation of 103 workers was undertaken. Data on age, sex, immune status, vaccination status and main work area were obtained from the medical officer administering the vaccination program and abattoir records. Symptoms and occupational risk factors for illness were obtained from interview of 63 (61%) employees. RESULTS: Of 103 abattoir employees, 16 (16%) had immunity from previous Q fever exposure and 19 (18 %) had been vaccinated at least six weeks before the first case of Q fever exposure in the abattoir. Of the remaining 68 workers who were susceptible to primary infection, 29 (43%) had laboratory confirmed acute primary Q fever and eight were suspected cases. No workers vaccinated before the likely period of exposure developed Q fever. Of 32 workers vaccinated post-exposure, four developed laboratory-confirmed Q fever within eight days of vaccination. Vaccination administered 10 or more days after the likely period of exposure showed no significant protective effect (RR=0.57; 95% CI 0.13-2.57; p=0.60). CONCLUSIONS: Q-Vax was highly effective when administered in advance of the likely period of Q fever exposure. Post exposure vaccination was not shown to be protective. IMPLICATIONS: This study reinforces meat industry vaccination guidelines for abattoir employees. The optimal time to vaccinate workers is before they are put at occupational risk.

Abattoirs↗

Immunogenicity and efficacy in aotus monkeys of four recombinant Plasmodium falciparum vaccines in multiple adjuvant formulations based on the 19-kilodalton C terminus of merozoite surface protein 1.

The immunogenicity and protective efficacy of four versions of recombinant C-terminal 19-kDa epidermal growth factor-like region of the major surface protein 1 (rMSP1(19)) of Plasmodium falciparum was studied in Aotus monkeys. Vaccination with each of the four rMSP1(19) constructs elicited high levels of antibodies to MSP1(19) but only one construct, the 19-kDa fragment expressed as a secreted fusion protein from Saccharomyces cerevisiae (yP30P2MSP1(19)), induced a high degree of protective immunity in Aotus nancymai against lethal P. falciparum challenge. Protective formulation required Freund's adjuvant; vaccination with yP30P2MSP1(19) in six other adjuvants that are suitable for human use induced lower levels of antibody response and no protection. These results emphasize the need to continue the search for an adjuvant that is comparable to Freund's adjuvant in potency and is safe for use in humans.

Adjuvants, Immunologic↗

Phase I trial of two recombinant vaccines containing the 19kd carboxy terminal fragment of Plasmodium falciparum merozoite surface protein 1 (msp-1(19)) and T helper epitopes of tetanus toxoid.

The safety and immunogenicity of 2 yeast-derived, blood-stage malaria vaccines were evaluated in a phase l trial. Healthy adults were given 2 or 3 doses of alum-adsorbed vaccine containing the 19 kDa carboxy-terminal fragment of the merozoite surface protein-1 (MSP-1(19)) derived from the 3D7 or the FVO strain of Plasmodium falciparum fused to tetanus toxoid T-helper epitopes P30 and P2. The first 2 doses of MSP-1(19) were well tolerated. Hypersensitivity reactions occurred in 3 subjects after the third dose of MSP-1(19), including bilateral injection site reactions in 2 (one with generalized skin rash), and probable histamine-associated hypotension in 1. Serum antibody responses to MSP-1(19) occurred in 5/16, 9/16 and 0/8 subjects given 20 microg of MSP-1(19), 200 microg of MSP-1(19), and control vaccines (hepatitis B or Td), respectively. Both MSP-1(19) vaccines were immunogenic in humans, but changes in formulation will be necessary to improve safety and immunogenicity profiles.

Adolescent↗

Characterization of human T- and B-cell epitopes in the C terminus of Plasmodium falciparum merozoite surface protein 1: evidence for poor T-cell recognition of polypeptides with numerous disulfide bonds.

We have investigated the relationship between cellular and humoral immune responses to defined epitopes of the C terminus of merozoite surface protein 1 (MSP-1) of the human malaria parasite, Plasmodium falciparum, in immune blood donors. Sera from almost all donors contained antibodies to the 33-kDa processing product of the MAD20 allele of MSP-1 (MSP-1(33)), but these antibodies did not cross-react with the equivalent sequence of the Wellcome allele. In contrast, T-cell responses to MSP-1(33) are directed towards epitopes that are conserved between the two allelic families. Only 50% of adult blood donors possessed antibodies which recognized the 19-kDa processing product of MSP-1 (MSP-1(19)). These antibodies predominantly recognized conserved epitopes involving both of the constituent epidermal growth factor-like domains of MSP-1(19). T-cell responses were found in only 26% (for recombinant proteins) or 44% (for synthetic peptides) of donors and were directed mainly at dimorphic sequences of the protein. There was no obvious association, at an individual level, between the presence of antibodies and the detection of T-cell proliferative or gamma interferon responses, suggesting that the T cells identified in this manner are not providing significant levels of help to B cells. T-cell responses to reduced recombinant proteins and linear peptides were more prevalent than responses to disulfide-bonded proteins, suggesting that the complex disulfide-bonded structure of native MSP-1(19) may inhibit antigen processing or presentation.

Amino Acid Sequence↗

Selective recognition of malaria antigens by human serum antibodies is not genetically determined but demonstrates some features of clonal imprinting.

Malaria infection induces the production of serum antibodies to a variety of malaria antigens but the prevalence of antibodies to any particular antigen is typically much less than 100%. It has been assumed that non-responsiveness to defined antigens in malaria immune subjects is due to HLS-mediated restriction of the immune response. In this study we have investigated the role of HLA and non-HLA genes in the antibody response to two merozoite surface antigens (MSP1 and MSP2) and a sexual stage antigen (Ps260/230) of Plasmodium falciparum, and conclude that host genotype is not a major determinant of responsiveness. Although antibody levels vary in accordance with seasonal variations in malaria transmission in semi-immune children, antibody levels remain stable in clinically immune adults. Antigen recognition is selective with individual donors showing consistent high titre responses to some antigens/epitopes whilst consistently failing to recognize adjacent regions/epitopes of the same protein. An alternative explanation, consistent with the data presented here, is that selective antibody responses to malaria antigens in immune individuals result from a process akin to clonal imprinting (original antigenic sin).

Adult↗

Thermotoga elfii sp. nov., a novel thermophilic bacterium from an African oil-producing well.

A thermophilic, glucose-fermenting, strictly anaerobic, rod-shaped bacterium, strain SEBR 6459T (T = type strain), was isolated from an African oil-producing well. This organism was identified as a member of the genus Thermotoga on the basis of the presence of the typical outer sheath-like structure (toga) and 16S rRNA signature sequences and its ability to grow on carbohydrates (glucose, arabinose, fructose, lactose, maltose, and xylose). Major differences in its 16S rRNA gene sequence, its lower optimum temperature for growth (66 degrees C), its sodium chloride range for growth (0 to 2.8%), its lack of lactate as an end product from glucose fermentation, and its peritrichous flagella indicate that strain SEBR 6459T is not similar to the three previously described Thermotoga species. Furthermore, this organism does not belong to any of the other genera related to the order Thermotogales that have been described. On the basis of these findings, we propose that this strain should be described as a new species, Thermotoga elfii. The type strain of T. elfii is SEBR 6459 (= DSM 9442).

Africa↗

The effect of irradiation on the third stage larvae of Brugia pahangi.

The effect of irradiation on the third stage larvae of the filarial nematode Brugia pahangi was investigated. Labelling with 35S methionine of control or irradiated L3, post-infective L3 or L4 revealed no consistent alterations in the pattern of proteins synthesized. The only significant difference observed was in 125I labelling, where the specific activity of labelling of soluble cuticular proteins was lower in irradiated than in control parasites. This difference may be related to the reduced size of irradiated parasites rather than to a specific effect of irradiation on the expression of cuticular proteins. Irradiated parasites recovered on day 14 post-infection were significantly shorter than control parasites. Irradiation also appeared to have a lethal effect on male parasites, as no recognizable males were recovered from animals given irradiated L3, nor were microfilariae ever observed in these animals. The mechanisms by which irradiation may enhance the immunogenicity of L3 of filarial nematodes are discussed.

Animals↗

The expression of small heat shock proteins in the microfilaria of Brugia pahangi and their possible role in development.

Development of the microfilariae of Brugia pahangi in the mammalian host is blocked until uptake by a mosquito vector when the developmental cycle is re-initiated. Comparison of the profile of polypeptides labelled in microfilariae cultured at mammalian temperature (37 degrees C) or mosquito temperature (28 degrees C) revealed a complex of low-molecular-weight proteins (18 kDa and 22-24 kDa) synthesized only in microfilariae at 37 degrees C. The synthesis of these proteins was also induced by transfer of microfilariae to 41 degrees C (i.e., heat shock conditions), suggesting that these are heat shock proteins. The expression of the small heat shock proteins in the Brugia life cycle is developmentally regulated, as they are not observed in the mature adult female. Their synthesis is strictly temperature dependent and is repressed upon transfer of the microfilariae to 28 degrees C.

Aedes↗

Duplex Doppler ultrasound for the detection of vascular occlusion following liver transplantation in children.

Sixty-three children and adolescent patients who received 78 consecutive orthotopic liver transplants and had serial duplex ultrasound monitoring were retrospectively reviewed for episodes of occlusion of the hepatic artery or portal vein. There were 13 documented episodes of complete occlusion of the main hepatic artery or a major branch, of which nine were diagnosed by the absence of flow during duplex ultrasound examination. Four occlusions were not detected, two affected hepatic artery branches, one an accessory hepatic artery, and one the main hepatic artery. The overall sensitivity of the method was 69% and specificity 100%. Six portal vein occlusions were documented in five patients and all six were successfully diagnosed on ultrasound examination, giving a sensitivity and specificity of 100%. Three of the patients had simultaneous occlusions of both vessels. In the early post-operative period duplex Doppler ultrasound examination has proved an effective non-invasive method for the detection of vascular occlusion, but is not yet sensitive enough to replace angiography fully for the detection of hepatic artery occlusion, particularly when this occurs distal to the main hepatic artery.

Adolescent↗

Enterotoxigenic aeromonads on retail lamb meat and offal.

Enrichment in alkaline peptone water was compared with the direct plating method for the isolation of Aeromonas spp. from lamb meat and offal samples. The enrichment method significantly increased the isolation rate of aeromonads. Motile Aeromonas species (A. hydrophila, A. sobria and A. caviae) were present in all kinds of samples investigated. Seventy-three Aeromonas strains isolated in this survey were characterized to species level and examined for their ability to produce virulence factors. Strains identified as A. sobria were the strongest producers of haemolysin and enterotoxin, whereas A. caviae strains were consistently non-haemolytic and non-enterotoxigenic. Thus it is likely that lamb meat and offal are potentially significant sources of virulent Aeromonas species and may play an important role in the aetiology of Aeromonas-associated gastro-enteritis.

Aeromonas↗

Infection control in the Department of Nuclear Medicine.

Concern about the spread of infections in the hospital setting has prompted regulatory agencies to mandate infection control standards. Each hospital department is required to have written policies and procedures which describe measures to prevent and control the spread of nosocomial infections (hospital acquired infections), along with quality assurance programs to assure that procedures are followed. The Department of Nuclear Medicine, as other departments, should have procedures which address special precautions for the prevention of nosocomial infections. This article will focus on a new approach to prevent nosocomial infections, guidelines for handling patients and contaminated equipment, and the importance of quality assurance activities to monitor compliance to established standards. An opening discussion on the routes of transmission, and factors necessary for transmission of infection, will serve as a review to assist with understanding the concept for handling the hospitalized patient in a Nuclear Medicine setting.

Acquired Immunodeficiency Syndrome↗

The acceptor for polar head groups of the lipid A component of Salmonella lipopolysaccharides.

We describe here experiments which determine at which stage in the lipid A biosynthesis the polar head groups 4-aminoarabinose, phosphorylethanolamine and 3-deoxy-D-manno-octulosonic acid are transferred to the diphosphorylated glucosamine backbone of the lipid A structure. Use was made of a conditional lethal mutant of Salmonella typhimurium (Ts1) which is defective in the synthesis of 3-deoxy-D-manno-octulosonic acid 8-phosphate and accumulates under nonpermissive conditions an underacylated lipid A intermediate [Lehmann, Rupprecht and Osborn (1977) Eur. J. Biochem. 76, 41-49]. Pulse-chase experiments, including a detailed analysis of radioactive pulse and chase products, demonstrated that this underacylated compound is a key intermediate in the lipid A synthesis. It can serve as direct acceptor for the incorporation of the polar head groups 4-aminoarabinose, phosphorylethanolamine and 3-deoxy-D-manno-octulosonic acid. On the basis of these findings some steps in the sequence of reactions involved in the lipid A biosynthesis are proposed.

Acetylglucosamine↗