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Biomedical subjects

S O'Donnell

Publications and source records attributed to S O'Donnell.

At least 37 records · Page 2Linked to original sources

Pulmonary toxicity following exposure to an aerosolized leather protector.

BACKGROUND: An aerosol spray for leather protection was reformulated to remove trichloroethane. The new formulation contained isobutane, n-heptane, ethyl acetate and fluoroaliphatics. RETROSPECTIVE REVIEW: Thirty-nine patients reported symptoms to the regional poison center. Respiratory symptoms developed within hours of exposure. Most symptoms resolved within two days. Abnormal pulmonary function tests, including obstructive disease or diminished diffusing capacity, were demonstrated in three of the four tested patients. CONCLUSIONS: The mechanism for the pulmonary toxicity has not been determined.

Acetates↗

An audit of 319 deaths across four general practices.

Death is a major outcome measure, and the value of an audit of the preventable factors leading to individual deaths is accepted in secondary care. Although approximately 20 of a typical general practitioner's patients will die every year, audits of deaths in general practice are seldom published. This is probably partly due to the difficulties posed by comparability, partly due to the wide range of causes of such deaths and possible contributory factors, and partly due to confidentiality considerations. We describe an audit of all death occurring in our practices over a 12-month period. Although cigarette smoking was considered to exceed all other contributory causes of death, preventable factors occurred in both primary and secondary care sufficiently often for important conclusions to be drawn. Comparison of causes of death between general practices is possible, and such enquiry can demonstrate important quality issues for both primary and secondary care.

Adolescent↗

Avulsion fracture of the anterior superior iliac spine presenting as acute-onset meralgia paresthetica.

Avulsion fracture of the anterior superior iliac spine is rare. Most cases occur in adolescents involved in competitive sports or vigorous exercise in which the sartorius and tensor fascia lata muscles are contracted strongly and suddenly against a hyperextended trunk. Patients who sustain this injury usually experience acute pain in the anterior pelvic region. We describe a patient with avulsion of the anterior superior iliac spine who presented with meralgia paresthetica. The symptoms resolved with conservative treatment.

Adolescent↗

Targeted accumulation of polyethylene glycol-coated immunoliposomes in infarcted rabbit myocardium.

The less than optimal accumulation of immunoliposome-associated reagents at target sites has often been attributed to the rapid in vivo clearance of immunoliposomes from the blood. In an attempt to overcome the drawback of rapid clearance and use the targeting potential of immunoliposomes, we have prepared long-circulating, 111In-labeled immunoliposomes. Targeting properties and enhanced circulation times were demonstrated in a rabbit model of acute experimental myocardial infarct. The specificity of liposomes for newly exposed intracellular cardiac myosin at the necrotic sites was achieved by incorporating monoclonal antimyosin antibody. Extended circulation times were achieved by cocoating the antimyosin-liposomes with polyethylene glycol (PEG). The half-life of the immunoliposomes was 40 min, which increased to 200 min with 4% mol PEG and to approximately 1000 min with 10% mol PEG. The degree of binding of modified immunoliposomes at the target sites was also dependent on the concentration of PEG incorporated at the liposome surface. This study demonstrates the accumulation of long-circulating targeted liposomes at the area of acute rabbit experimental myocardial infarction.

Animals↗

Safety and immunogenicity in North Americans of a single dose of live oral cholera vaccine CVD 103-HgR: results of a randomized, placebo-controlled, double-blind crossover trial.

We conducted a double-blind, placebo-controlled, randomized crossover study to evaluate the safety and immunogenicity of a single 5 x 10(8)-CFU dose of live oral recombinant cholera vaccine CVD 103-HgR in 94 North American adults. The vaccine was well tolerated without associated adverse reactions. Despite minimal fecal excretion of vaccine, 97% of subjects exhibited serum vibriocidal antibody and 72% had antitoxin responses.

Administration, Oral↗

Posterior cruciate condylar total knee arthroplasty. Average 11-year follow-up evaluation.

Forty-two total knee arthroplasties (TKAs) of the posterior cruciate condylar design performed from 1975 until 1978 were reviewed. Follow-up evaluations averaged 11 years. There were 21 knees each of osteoarthrosis and rheumatoid arthritis. The average postoperative knee score was 85.4 points. Thirty-nine knees (92.8%) were rated good or excellent, one (2.4%) was judged fair, and two (4.8%) were considered failures. Postoperative flexion averaged 104 degrees. Analysis of osteoarthritic versus rheumatoid arthritic subgroups demonstrated no significant differences in motion, alignment, or knee score. Roentgenographic review demonstrated no cases of femoral or tibial loosening, but one case of patellar component dislodgement was observed. Nonprogressive radiolucent lines were observed in 75% of the cases. Good results can be expected if satisfactory lower-extremity alignment is attained. Posterior cruciate ligament retention has provided a slightly improved postoperative range of motion. Residual problems appear to be centered about the patellofemoral joint.

Adult↗

Association between O blood group and occurrence and severity of diarrhoea due to Escherichia coli.

During studies of diarrhoea due to Escherichia coli in 316 adult volunteers, ABO and Rh blood group determinations were done to look for differences in the occurrence or severity of illness in association with certain blood groups. In studies using heat-labile enterotoxin-producing E. coli, volunteers with O blood group had a significantly higher attack rate for diarrhoea than persons with other blood groups. In contrast, in studies with enteropathogenic or heat-stable enterotoxin-producing E. coli, no association was found between occurrence of diarrhoea and ABO group. These studies, and previous studies finding a similarly increased susceptibility to cholera in persons with O blood group, suggest that the mechanism of increased risk involves an interaction between blood group substances and the similar enterotoxin produced by E. coli and Vibrio cholerae.

ABO Blood-Group System↗

Antenatal education: does it improve the quality of labour and delivery?

Of 196 nulliparous women who delivered in a two month period, 78 percent had attended antenatal education classes. The mothers who did not attend antenatal classes consisted of significantly more Maori and Pacific Island mothers, they were younger, smoked more, had a lower socioeconomic status and fewer were married. The group who went to antenatal education classes had a significantly longer second stage in labour and required more forceps assistance during delivery compared to non-attenders. These results remained for the polynesian mothers, when they were analysed separately and the differences in age and socioeconomic status were no longer present. There was no difference in the type of pain relief required during childbirth by the attenders or non-attenders. We found no evidence that attending antenatal education classes will ensure an easy and less complicated childbirth.

Age Factors↗

Dose response of A/Alaska/6/77 (H3N2) cold-adapted reassortant vaccine virus in adult volunteers: role of local antibody in resistance to infection with vaccine virus.

An attenuated influenza A candidate vaccine virus, derived from the A/Ann Arbor/6/60 (H2N2) cold-adapted (ca) donor virus and the A/Alaska/6/77 (H3N2) wild-type virus, was evaluated in adult seronegative volunteers (serum hemagglutination-inhibiting antibody titer, less than or equal to 1:8) for level of attenuation, infectivity, antigenicity, and genetic stability. Four groups with similar preinoculation mean titers of serum and nasal wash antibodies were inoculated intranasally with 10(4.5), 10(5.5), 10(6.5), or 10(7.5) 50% tissue culture infectious doses (TCID50) of the ca reassortant virus, and eight other seronegative adult volunteers received the wild-type virus. Only 2 of 66 vaccinees developed fever or mild and brief systemic or upper respiratory tract illness or both. Both volunteers with vaccine-related reactions received the highest dose (10(7.5) TCID50) of ca virus, which indicates that the vaccine retains some mild reactogenicity at a high dosage. In contrast, four of eight volunteers infected with the wild-type virus became ill. Each of the 54 isolates tested retained the temperature-sensitive phenotype of the vaccine virus. Thus, the ca reassortant was genetically stable and attenuated at 10(4.5) to 10(7.5) TCID50 for seronegative adults. The 50% human infective dose of ca virus was approximately 10(5.3) TCID50. Ten and one hundred 50% human infectious doses infected 73 and 83% of vaccinees, respectively, and approximately 75% developed an immunological response at these doses. The failure of the vaccine virus to infect some volunteers was correlated with the presence of pre-inoculation nasal wash immunoglobulin A hemagglutinin antibody.

Adult↗

Immunogenicity of Ty21a attenuated "Salmonella typhi" given with sodium bicarbonate or in enteric-coated capsules.

Ty21a, a stable attenuated mutant of Salmonella typhi, is a safe, protective oral vaccine when 3 doses of 10(9) cells in saline are taken after neutralization of gastric acidity by 1 g NaHCO3. To identify a more convenient method to administer vaccine and to determine the feasibility of immunizing with a single dose, we studied the immune response of children and adults to different formulations of Ty21a with a newly developed, sensitive, enzyme-linked immunosorbent assay (ELISA). In this ELISA, a rise in S. typhi O antibody was defined as a change in net optical density of greater than or equal to 0.15 (more than 3 SD from the mean difference in optical density in a negative control population). Three hundred and thirty-five Chilean children were given 3 doses of 10(9) Ty21a in 150 ml of milk with 0.8 g NaHCO3 or in enteric-coated capsules. In each group, 5% seroconverted by Widal O but 41% by IgG ELISA O antibody titers; mean antibody levels by group were identical. Studies were also carried out in healthy college students in a non-endemic area (U.S.A.) who had no history of prior typhoid immunization. In total, 141 U.S. adults received vaccine formulated in either one of two ways: 1) in gelatin capsules administered with two additional gelatin capsules containing a total of 0.8 gm NaHCO3 or 2) in enteric-coated capsules. Thirty-six persons received one dose, 30 got two doses and 16 ingested three doses of enteric-coated vaccines, while 44 persons receiving one dose and 15 got two doses of vaccine in the gelatin capsule formulation. Rates of seroconversion of ELISA O antibody were similar in all the groups. Ty21a vaccine was not recovered from multiple stool, jejunal fluid or blood cultures of the U.S. vaccine recipients. Based on these observations a large-scale field trial of efficacy has been initiated in 90.000 schoolchildren 6-20 years of age in Santiago, Chile, of whom one-third received one dose of enteric-coated vaccine, one-third got two doses and the remainder received placebo.

Adolescent↗

Reactogenicity, immunogenicity and efficacy studies of Escherichia coli type 1 somatic pili parenteral vaccine in man.

Purified type 1 somatic pili from enterotoxigenic Escherichia coli (ETEC) strain H10407 (O78:H11) was evaluated as a parenteral immunizing agent in the hope that this antigen might enhance a contemplated polyvalent pilus vaccine. Intramuscular inoculation with 45, 90, 900 or 1 800 mcg of pili vaccine was tolerated without incident in 82 volunteers. Six of 15 persons who received a 28 day booster of 1 800 mcg developed local reactions while none of 52 persons receiving 180 or 450 mcg boosters evinced such reactions. Pili vaccine did not significantly alter intestinal transit time, absorptive capacity or the prevalence of colonic E. coli bearing type 1 somatic pili of the H10407 antigenic variety. All vaccinees developed significant rises in circulating IgG antibody to type 1 somatic pili, the magnitude of the response being directly proportioned to the vaccine dose. None of the vaccinees had significant rises to CFA I or II pili nor to heat-labile enterotoxin. However, many had rises in O antibody, particularly among those inoculated with 1 800 mcg. Three challenge studies were carried out with E. coli H10407 to assess vaccine efficacy. In the initial study the vaccinees were either protected against diarrhea (2 of 6 vaccinees versus 7/7 of controls) or had milder disease than the controls. In two subsequent challenges with H10407 significant protection was not seen. It was not clear whether protection exhibited by the vaccinee group in the first challenge was due to O antibody, pili antibody, or both acting synergistically. To clarify this, a group of the immunized volunteers were challenged with ETEC strain B7A which is a different serotype (O148:H28) lacks CFA/I or II pili, but possesses type 1 somatic pili antigenically distantly related to those of H10407. Attack rates and severity of illness were similar in both vaccinee and control groups. While most volunteers challenged with E. coli H10407 developed significant rises in circulating antibody to CFA/I, LT and O antigen, none had rises to type 1 somatic pili. It is unclear if this is due to immune tolerance to this antigen when encountered enterally or whether these pili are not present in vivo in ETEC initiating diarrhea in the proximal small intestine. In summary, parenterally inoculated type 1 somatic pili were safe and highly immunogenic in man but did not consistently induce protection. Further studies are planned to clarify the role of antibody to type 1 somatic pili in mediating protection.

Adult↗

Structure of a 7Fe ferredoxin from Azotobacter vinelandii.

The structure of the 7Fe ferredoxin from Azotobacter vinelandii has been solved from a 3.0-A multiple isomorphous replacement map. The crystals belong to space group P43212 with a = 55.22, c = 95.20 A, and Z = 1. Heavy-atom derivatives were prepared with K2PtCl4,K2[OsO2(OH)4], and Na3RhCl6. Anomalous scattering data were collected for native (Fe) and Pt derivative crystals. The figure of merit for 3,322 reflections to 3.0 A is 0.74. The structure consists of an NH2-terminal core of residues 1-50 which form the Fe-S cluster sites, and a COOH-terminal chain of residues 51-107 which wraps around this core. The [3Fe-3S] cluster is ligated by cysteines 8, 11, 16, 20, and 49 and a sixth ligand which is either glutamic acid 18 or an exogenous small molecule. The [4Fe-4S] cluster is ligated by cysteines 24, 39, 42, and 45. The coordination of both Fe-S centers has been confirmed by fitting of the cluster atoms and residues 1-50 to unbiased 2Fo-Fc Fourier maps at 2.5-A resolution. The structure of the 3Fe center has also been confirmed with anomalous scattering difference Fourier maps using both isomorphous replacement and refined phases. The partially refined structure at 2.5 A (3,490 reflections, 6.0 sigma(F)) has R = 35%.

Azotobacter↗