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1.  Rickettsial Endocarditis 
British Medical Journal  1963;2(5352):320.
PMCID: PMC1872396
2.  Vaccine prophylaxis of abattoir-associated Q fever: eight years' experience in Australian abattoirs. 
Epidemiology and Infection  1990;104(2):275-287.
During the period 1981-8 a clinical trial of a Q fever vaccine (Q-vax; Commonwealth Serum Laboratories, Melbourne) has been conducted in abattoir workers and other at-risk groups in South Australia. Volunteers in four abattoirs and visitors to the abattoirs were given one subcutaneous dose of 30 micrograms of a formalin-inactivated, highly-purified Coxiella burnetii cells, Henzerling strain, Phase 1 antigenic state, in a volume of 0.5 ml. During the period, over 4000 subjects have been vaccinated and the programme continues in the abattoirs and related groups. 'Common' reactions to the vaccine comprised tenderness and erythema, rarely oedema at the inoculation site and sometimes transient headache. Two more serious 'uncommon' reactions, immune abscess at the inoculation site, were observed in two subjects, and two others developed small subcutaneous lumps which gradually dispersed without intervention. Protective efficacy of the vaccine appeared to be absolute and to last for 5 years at least. Eight Q fever cases were observed in vaccinees, but all were in persons vaccinated during the incubation period of a natural attack of Q fever before vaccine-induced immunity had had time (greater than or equal to 13 days after vaccination) to develop. On the other hand, 97 Q fever cases were detected in persons working in, or visiting the same abattoir environments. Assays for antibody and cellular immunity showed an 80-82% seroconversion after vaccination, mostly IgM antibody to Phase 2 antigen, in the 3 months after vaccination. This fell to about 60%, mostly IgG antibody to Phase 1 antigen, after 20 months. On the other hand, 85-95% of vaccinees developed markers of cell mediated immunity as judged by lymphoproliferative responses with C. burnetii antigens; these rates remained elevated for at least 5 years. The Q fever vaccine, unlike other killed rickettsial vaccines, has the property of stimulating long-lasting T lymphocyte memory and this may account for its unusual protective efficacy as a killed vaccine.
PMCID: PMC2271744  PMID: 2323360
3.  Prevalence of antibody to hepatitits B surface antigen among staff in an Edinburgh hospital. 
The Journal of Hygiene  1977;78(1):57-68.
Antibody to hepatitis B surface antigen was detected by radioimmunoprecipitation in 74 (5-5%) of 1336 staff members in a large general hospital in Edinburgh, in 14 (2-9%) of 480 volunteer blood donors in the area, and in 12 (6-1%) of 197 pregnant women attending for the first time at the ante-natal clinic in the hospital. Rates of antibody prevalence rose with age in the sample of hospital staff and in that of the blood donors, particularly among males. On the other hand, in the ante-natal patients antibody prevalence declined with age. The rates in hospital staff were higher than those in blood donors of comparable age and sex, and high titres of antibody were more common in the staff group. However, no association was found between antibody prevalence and a history of clinical hepatitis, blood transfusion, or recognized contact with cases of hepatitis. Staff who had previously worked in an infectious disease hospital did not show increased antibody prevalence, indicating that simple isolation measures have been adequate to minimize exposure to hepatitis B. No particular prevalence of infection was seen in physicians and surgeons, in the nursing staff, or in workers in clinical diagnostic laboratories, hospital administration or other areas. One group clearly showing increased antibody prevalence was staff currently working, or who had worked, in the Haemodialysis Unit; this correlated with the outbreak of dialysis-associated hepatitis in 1969--70. However, no evidence suggested that significant dissemination of infection had occurred to other defined groups of hospital staff. Elevated rates were also observed in a small sample of kitchen and portering staff, and in obstetric medical and nursing staff; the latter observation indicate a need for further investigation to identify unsuspected exposure to hepatitis B virus.
PMCID: PMC2129744  PMID: 264499
8.  Laboratory diagnosis of Mycoplasma pneumoniae infection. 4. Antigen capture and PCR-gene amplification for detection of the Mycoplasma: problems of clinical correlation. 
Epidemiology and Infection  1992;109(3):519-537.
Direct detection assays for Mycoplasma pneumoniae were established by PCR amplification of short sequences within the foot protein/adhesin (P1) gene and the 16S ribosomal RNA gene. Specificity and sensitivity was excellent, no hybridization was observed with M. genitalium and other human Mycoplasma species. In nose and throat washings from subjects with respiratory infection a pattern of high counts (c.f.u./ml) of M. pneumoniae (deduced from the amount of amplified PCR product), and a positive antigen capture assay, was found in 83% of subjects with serological evidence of current infection with M. pneumoniae. A small proportion of subjects with serological patterns suggesting infection in the more distant past had positive PCR assays. This was considered to represent either persistence of the organism from a previous infection or perhaps transient carriage during a reinfection, without substantial change in antibody response. PCR-based assay of M. pneumoniae offers a powerful, rapid, and sensitive substitute for culture of the mycoplasma. Antigen capture, while less sensitive than PCR, offers the advantage that it is more often positive with samples from current infection and requires less stringent laboratory organization to contain false positive results. We conclude however that the laboratory diagnosis of a chosen clinical episode should not rest on the PCR or Ag-EIA assays alone, but must also include antibody assays to confirm whether infection is current or represents persistence from past exposure.
PMCID: PMC2271932  PMID: 1281781
9.  Laboratory diagnosis of Mycoplasma pneumoniae infection. 3. Detection of IgM antibodies to M. pneumoniae by a modified indirect haemagglutination test. 
Epidemiology and Infection  1989;103(3):613-623.
The indirect haemagglutination (IHA) test was compared with the complement-fixation (CF) test for the measurement of antibodies to Mycoplasma pneumoniae. A modification of the IHA was used to measure M. pneumoniae IgM antibodies. Sera were obtained from various groups of patients who were either culture or antigen positive for M. pneumoniae in nasopharyngeal aspirates or who had fourfold or greater increase in CF antibody or a titre greater than or equal to 320. The results of these comparisons showed that the modified IHA test was specific and more sensitive (89% as opposed to 64%) than the CF test. The modified IHA test for the detection of IgM antibody was highly effective in the recognition of recent or current infection with the mycoplasma. It was also of equal sensitivity to an indirect enzyme immunoassay for the detection of IgM antibodies to M. pneumoniae.
PMCID: PMC2249550  PMID: 2514114
10.  Laboratory diagnosis of Mycoplasma pneumoniae infection. 1. Direct detection of antigen in respiratory exudates by enzyme immunoassay. 
Epidemiology and Infection  1988;101(3):669-684.
Direct and indirect antigen capture enzyme immunoassays (Ag-EIA) have been developed for the detection of Mycoplasma pneumoniae in nasopharyngeal aspirates or sputum from respiratory infection. The sensitivity of the two Ag-EIA were similar, but the indirect method using polyclonal rabbit and guinea-pig antisera was more convenient. The Ag-EIA had a detection limit of 10(4-4.5) colony-forming units/ml of sample. It was specific for M. pneumoniae and gave a low level response with M. genitalium. There were no cross-reactions with 10 other species of mycoplasmas. Tests with a wide range of bacteria and chlamydia group antigen, representing agents sometimes found in the respiratory tract, were also negative. At the current level of development, the Ag-EIA detected about 90% of specimens that were also positive for culture; 43% of specimens from culture-negative--seropositive patients gave a positive result. The overall pattern of results indicated that while antigen detection is a quick and effective substitute for the slow culture method, serological examination for specific IgM antibody is also necessary to give a complete diagnostic coverage.
PMCID: PMC2249410  PMID: 3145891
11.  Laboratory diagnosis of Mycoplasma pneumoniae infection. 2. Comparison of methods for the direct detection of specific antigen or nucleic acid sequences in respiratory exudates. 
Epidemiology and Infection  1988;101(3):685-694.
The efficiency of the direct detection of Mycoplasma pneumoniae in respiratory exudates by an antigen capture, indirect enzyme immunoassay (Ag-EIA), has been compared with its detection with a cDNA probe ('Gen-Probe assay') directed against the specific ribosomal RNA sequences of the organism ('Mycoplasma pneumoniae Rapid Diagnostic System', Gen-Probe, San Diego, California). Both assays showed excellent specificity against a range of mycoplasma species suspended in negative nasopharyngeal aspirates; only M. pneumoniae and M. genitalium reacted. In experiments with graded doses of viable M. pneumoniae cells suspended in negative nasopharyngeal aspirate, the Gen-Probe assay was more sensitive than Ag-EIA; detection limits were respectively 2 X 10(3) c.f.u./ml (3.2 X 10(5) genomes) and 2.5 X 10(4) c.f.u./ml (4 X 10(6) genomes); detection levels 10-100 times less sensitive than culture. The two assays were also tested on nasopharyngeal aspirates or sputum specimens from 90 patients with respiratory infection; 67 of these were culture- or seronegative for M. pneumoniae and 23 were culture- or seropositive. Ag-EIA detected 21 (91%) of the latter but the Gen-Probe assay detected only 5 (22%). Both assays were negative with the 67 culture-/sero-negatives; there were no Gen-Probe assay positive/Ag-EIA negatives. Overall, it is concluded that although Ag-EIA and the Gen-Probe assay are effective substitutes for culture as a diagnostic procedure, there is a significant problem with samples which are culture-negative and from patients who have good serological evidence of current infection. Possible reasons for the disparity between the two assays are advanced.
PMCID: PMC2249409  PMID: 3145892
12.  Rheumatoid polyarthritis after rubella. 
Annals of the Rheumatic Diseases  1978;37(3):266-272.
A 21-year-old woman developed persistent polyarthritis indistinguishable from rheumatoid arthritis after rubella. The arthritis persisted for approximately 30 months and was associated with high levels of antibody to rubella virus and with rheumatoid factor. The antibody titres declined pari passu with clinical improvement which progressed to complete resolution. Fractionation of serial serum specimens showed a substantial and persistent IgM antibody response to rubella virus. Rubella antigen was not demonstrated in the synovial exudate.
PMCID: PMC1000220  PMID: 686860
13.  Rubella virus and rheumatoid arthritis. 
A collection of synovial fibroblasts from 19 patients with rheumatoid arthritis (RA) and 12 patients with osteoarthrosis or other non-RA disease has been examined for rubella virus antigens by immunofluorescence and radioimmunoassay with negative results. Eluates of synovial membrane prepared under conditions likely to dissociate antigen-antibody complexes have shown no rubella antibody. A serological survey of RA patients and those with other forms of arthritis has shown no differences in the frequency or levels of rubella haemagglutination-inhibiting antibody. These results provide little support for various hypotheses that a persistent infection with rubella virus underlies or initiates the rheumatoid process.
PMCID: PMC1006622  PMID: 320944
14.  Cytology of rheumatoid synovial cells in culture. IV. Further investigations of cell lines cocultivated with rheumatoid synovial cells. 
Annals of the Rheumatic Diseases  1976;35(4):297-305.
A previous report described a cell isolate presumed to have arisen by accidental cocultivation (contamination) of the Chang 'liver' cell line and rheumatoid synovial cells. This cell isolate had the same glucose-6-phosphate dehydrogenase isoenzyme as the Chang cell and also some shared antigens. It clearly differed in its karyotype, its ability to grow in semisolid agar, and in the possession of bleb-like projections of the cytoplasmic membrane filled with collections of beaded or granular material. In addition, it had a novel antigen(s) not present in the Chang cell. As these properties might have been acquired from the synovial cells and because the bleb structures resembled those seen in some cell lines transformed by leucovirus the cell isolate has been further studied. Cytochemical methods at the light and electron microscope level showed that the granular material was polysaccharide in nature, probably glycogen. No evidence was found of the presence of a virus or a viral genome using a variety of techniques including attempted induction followed by 3H-uridine labelling of the cultures, and assay of the supernatant fluid from the culture for viral RNA-dependent DNA polymerase. In addition, cell extracts were not found to contain viral RNA-dependent DNA polymerase or RNA-dependent RNA polymerase. No rubella virus or leucovirus interspecies antigens were detected on the cell membranes.
PMCID: PMC1007386  PMID: 184745
15.  Attempts to identify viruses in rheumatoid synovial cells. 
Annals of the Rheumatic Diseases  1976;35(2):106-113.
Synovial fibroblast cell strains derived from the synovial membranes of 7 patients with rheumatoid arthritis were examined for the presence of viruses, in particular leucoviruses. Seven similar synovial strains derived from patients with other arthritic conditions were used as a control group. Evidence of the presence of a virus or a viral genome was looked for by several methods of induction followed by 3H-uridine labelling of the cultures. In addition, the culture supernatant, after induction and after the synovial strains had been co-cultivated with a variety of cell lines from several species, was assayed for the presence of viral RNA-dependent DNA polymerase activity. The DNA-polymerase activity of the synovial cells themselves was also determined. No evidence was found by any of these techniques to indicate the presence of virus or viral information within the synovial fibroblasts.
PMCID: PMC1006519  PMID: 60087
16.  DNA polymerase activity in rheumatoid synovial membranes. 
Annals of the Rheumatic Diseases  1975;34(3):205-212.
RNAase-sensitive DNA polymerase activity was demonstrated in synovial membrane preparations from 23 out of 25 rheumatoid arthritis patients. Control groups consisted of twelve patients with osteoarthrosis, four with secondary osteoarthrosis, and twelve with other conditions. The last group showed no activity, while the results with the other two groups were varied. The properties of the polymerase enzyme, such as its stimulation by synthetic templates and inhibition by actinomycin D, were not consistent with it being associated with an oncogenic virus; it seems to be more like that found in stimulated normal human lymphocytes, described as an RNA-primed DNA-directed DNA polymerase.
PMCID: PMC1006398  PMID: 1155979
19.  The effect of gold salts on tumour immunity and its stimulation by Corynebacterium Parvum. 
British Journal of Cancer  1975;32(5):558-567.
The anti-inflammatory agent sodium aurothiomalate appears to act upon mononuclear phagocytes, inhibiting their lysosomal enzyme activity. Evidence is presented that gold salts can increase the number of lung tumour nodules that develop following intravenous injection of tumour cells and pretreatment can enhance the take of a subcutaneous tumour inoculum. In contrast, they do not affect the later growth of tumour. Gold salts can also suppress the action of systemically administered C. parvum in inhibiting the growth of subcutaneous tumours. These results are taken as supporting the evidence in favour of a fast acting nonspecific anti-tumour mechanism, probably macrophage mediated, that can be inhibited by gold salts and enhanced by C. parvum. The effect of gold salts upon other biological changes induced by C. parvum is examined, including its adjuvant action, and the results are discussed in the context of the mechanisms underlying the immunotherapeutic action of this organism.
PMCID: PMC2024804  PMID: 813755
20.  Rheumatoid Arthritis, Rheumatoid Factor, and Tests for Australia or Hepatitis-associated Antigen 
British Medical Journal  1972;4(5831):23-24.
False-positive results in tests for hepatitis-associated antigen using latex agglutination techniques may be due to rheumatoid factor in the serum. Possibly the use of IgM antibody in preparing the latex particles might diminish the occurrence of such reactions. No evidence was found for a relation between rheumatoid arthritis and a significant incidence of hepatitis-associated antigen detectable by countercurrent immunoelectro-osmophoresis.
PMCID: PMC1786123  PMID: 5078408
23.  Eaton Agent 
British Medical Journal  1960;1(5179):1137-1138.
PMCID: PMC1966968
24.  Q fever in Great Britain 
The Journal of Hygiene  1956;54(1):118-140.
PMCID: PMC2217995  PMID: 13319698

Results 1-25 (43)