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Biomedical subjects

P D Griffiths

Publications and source records attributed to P D Griffiths.

At least 307 records · Page 17Linked to original sources

Comparison of enzyme-linked immunosorbent assay, radioimmunoassay, complement fixation, anticomplement immunofluorescence and passive haemagglutination techniques for detecting cytomegalovirus IgG antibody.

The radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) techniques were found to be comparable in sensitivity and specificity for detecting cytomegalovirus IgG antibody, and 10 to 100 times more sensitive than complement-fixation (CF), anticomplement immunofluorescence (ACIF) and passive haemagglutination (PHA). In screening tests for antibody, the frequency of false-positive and -negative results was 0.6% for RIA and ELISA, 1.5% for CF, 1.6% for ACIF and 3.6% for PHA. PHA was the least satisfactory test, largely because of technical problems. Cytomegalovirus (CMV) infection is an important cause of congenital brain damage and is also a major complication of both prolonged immunosuppressive therapy, especially in patients with organ transplants, and multi-donor blood transfusions. For serological diagnosis of infection, as well as for screening for antibody in patients and in blood donors, the solid-phase indirect radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) techniques offer distinct improvements in sensitivity over previous methods. Although the principle of both tests, based on the detection of antigen-antibody reactions by means of a labelled anti-antibody, is the same, each possesses its own particular technical advantages and disadvantages, and both require their own expensive equipment for the reading of the results. There is still a lack of data on how they compare in sensitivity and specificity. The present study was undertaken to compare the two methods for the detection of CMV IgG and to evaluate them against the older techniques of complement-fixation (CF), passive haemagglutination (PHA) and anticomplement immunofluorescence (ACIF).

Antibodies, Viral↗

Congenital cytomegalovirus infection: diagnostic and prognostic significance of the detection of specific immunoglobulin M antibodies in cord serum.

Specific immunoglobulin M antibodies were detected by radioimmunoassay (RIA-IgM) in cord sera from 83/93 (89%) babies congenitally infected with cytomegalovirus (CMV) but in 0/104 cord sera from uninfected control subjects. The type of maternal infection did not affect the ability of the assay to identify congenital infections, but increased RIA-IgM titers were found more frequently in cord sera from babies infected following primary CMV infections (9/18; 50%) than following recurrent CMV infections (1/12; 8%) (P less than .05). The magnitude of the fetal immune response was related to disease inasmuch as 14/40 (35%) babies with increased RIA-IgM titers were symptomatic at birth compared with 1/43 (2%) with lower titers (P less than .001). When combined with the results of testing for rheumatoid factor and total IgM, the RIA-IgM assay defined subgroups of babies with generally poor (7/15; 47% symptomatic at any stage) or generally good (0/21 symptomatic) prognoses. Prospective studies currently identifying cases of congenital CMV infection may wish to use these three serologic techniques as the results obtained appear to have prognostic significance for those babies who are initially asymptomatic.

Antibodies, Viral↗

The presumptive diagnosis of primary cytomegalovirus infection in early pregnancy by means of a radioimmunoassay for specific-IgM antibodies.

During a 30 month investigation 3633 women were studied when the booked for antenatal care. Complement fixing antibodies against cytomegalovirus (CMV) were detected in 2078 (57 per cent) of the women and these sera were further tested for the presence of specific IgM antibodies by means of a solid-phase radioimmunoassay. Since specific IgM antibodies have previously been shown to persist for up to four months after primary CMV infection, their presence in a booking serum sample (mean gestation 15 weeks) was taken as presumptive evidence of a first trimester primary CMV infection. From theoretical considerations, 11.6 positive CMV-IgM reactions were predicted in these women and 11 were observed. A highly significant (p less than 0.001) excess of fetal death was seen in the infected women since three pregnancies ended in missed abortion (15 weeks), intrauterine death (29 weeks) and spontaneous abortion (24 weeks) whilst the remaining 8 women gave birth to apparently normal babies. Cord sera were available from 5 of the surviving babies and only one contained specific IgM antibodies, showing that transplacental spread of the maternal infections had not occurred in 4 of the 5 survivors.

Antibodies, Viral↗

Limitations concerning the use in children of the relationship between plasma creatinine and body height to derive glomerular filtration rate.

The value of the formula, (Formula: see text) was assessed over a two-year period in 314 children aged 1 month to 17 years by comparing simultaneously determined 51Cr EDTA slope clearance and plasma creatinine measurements, and in 225 children aged 1 month to 16 years comparing with duplicate short-term creatinine clearance determinations. The relationship with 51Cr EDTA slope clearance is best in patients over the age of 3 years with clearance rates below 60 ml. min-1/1.73m2 but even so is subject to doubt over a wide range. The relationship with creatinine clearance shows less scatter at higher levels of clearance but the same doubt exists when it is used as an estimate of glomerular filtration rate.

Adolescent↗

Coxsackie B virus infections and myocardial infarction. Results from a prospective, epidemiologically controlled study.

During an eight-month study, acute serum samples were obtained from all 228 patients admitted with chest pain to a coronary-care unit. On admission a history of a recent influenza-like illness was given by the same proportion (5%) of those subsequently shown to have myocardial infarction, angina, or miscellaneous diagnoses. Myocardial infarction was diagnosed in 105 patients and serum samples were obtained from all of the 93 survivors during convalescence. Sera were also obtained from 99 age and sex matched controls from the same geographical area. Sera from the cases and controls were tested for Coxsackie B antibodies by microneutralisation. In 3 patients with MI and 2 controls significant increases in antibody titre occurred which indicated recent infection. The distribution of type-specific antibodies, geometric mean titres, seropositivity rates, and the prevalence of raised antibody titres were all identical in the cases and the controls. These results do not accord with observations in uncontrolled series which suggested a causal relation between infections with Coxsackie B viruses and myocardial infarction.

Adult↗

Persistence of high titre antibodies to the early antigens of cytomegalovirus in pregnant women.

Serial serum samples were obtained from 45 pregnant women who had been shown to possess complement fixing (CF) antibodies to cytomegalovirus (CMV) during a previous pregnancy. The serial samples were tested for antibodies against the early antigens (EA) and complement fixing antigens of CMV. All of the 45 women still possessed CF antibodies at the commencement of their next pregnancy. Six of the 45 women (13 per cent) lacked detectable IFA-EA antibodies whilst 19/45 (42 per cent) women possessed only low titres (less than or equal to 64) of these antibodies. However, 20/45 (44 per cent) women possessed high titre (greater than or equal to 128) antibodies despite having experienced their primary CMV infection many months previously. It is concluded that antibodies to the EA OF CMV are not as transitory as has been suggested and that their presence, even at high titre, in a serum sample from a pregnant woman cannot be taken as presumptive evidence of recent primary infection with this virus.

Antibodies, Viral↗

A prospective study of primary cytomegalovirus infection in pregnant women.

During a four year study, sera were obtained from 5575 women attending for antenatal care and 3188 (57.2 per cent) were shown to possess complement fixing antibodies to cytomegalovirus (CMV). A total of 1608 seronegative women were followed to term and 14 (0.87 per cent) primary CMV infections occurred in either the second or third trimester. Transplacental spread of CMV occurred in 3 out of 12 (25 per cent) of the 14 babies born to infected mothers. All 14 babies were apparently normal at birth but short term clinical follow-up has already revealed that one child has impaired hearing whilst another is microcephalic. The women were also monitored serologically throughout pregnancy for evidence of rubella infections. Only 12 infections were detected and 7 of these occurred during the large rubella epidemic of 1978. Of the 10 pregnancies which were allowed to proceed to term, transplacental spread of rubella virus occurred in 1 out of 7 (14 per cent). During this study period, CMV infections occurred as frequently as did rubella infections. We therefore conclude that, apart from those years when extensive epidemics occur, many more pregnant women are infected with CMV than with rubella virus.

Cytomegalovirus Infections↗

A prospective study of influenza infections during pregnancy.

Serological evidence of infection with influenza A and B viruses was sought during three successive winters. Paired sera from 1595 pregnant women were studied and 79 infections occurred in 77 women (4.8%). A further 77 women who had no serological evidence of recent influenza infection were selected from the study population to serve as a control group. Cases and controls were comparable with respect to age, race, marital status, and number of previous pregnancies. Their offspring had virtually identical mean birth weights, skull circumferences, lengths, and incidences of neonatal jaundice. Although all the infections occurred in either the second or the third trimesters of pregnancy, the cases delivered more babies with congenital abnormalities than did the controls. The possibility was considered that the presence of an abnormal fetus made these women more susceptible to influenza infection. Unexpectedly, the women experiencing influenza infection during pregnancy delivered an excess of male babies, and an excess of females was born to the controls. Although this difference was statistically highly significant (P < 0.01), a biological explanation for the results was not readily apparent and it is suggested that future studies of influenza during pregnancy should particularly look for evidence of an altered sex ratio.

Birth Weight↗

Chlamydia, cytomegalovirus, and Yersinia in inflammatory bowel disease.

The relationship of three infectious agents, Chlamydia, cytomegalovirus, and Yersinia enterocolitica, to the aetiology, clinical course, and diagnosis of Crohn's disease was studied. There was no evidence of chlamydial infection in Crohn's disease and no indication either that cytomegalovirus alters the outcome of acute attacks or that infection with Y. enterocolitica is being misdiagnosed as Crohn's disease.

Acute Disease↗

A longitudinal study of the serological and virological status of 18 women infected with cytomegalovirus.

18 women, of known seropositivity, have been followed for between 18 and 66 months (mean 50.2 months) for viral excretion and serological changes. CMV was isolated from 58/146 (39.7 per cent) cultures from various sites, mostly cervix. A total of 129 sera were obtained and each was titrated in the late antigen, early antigen and anti-complement immunofluorescence assays, as well as the complement fixation and microneutralisation tests. From 3 women virus was consistently re-isolated, from 3 others virus was never re-isolated and the remaining 12 women excreted virus intermittently during the period of study. No significant changes in antibody titres could be detected by any of the 5 serological assays in any woman during periods of viral excretion. This suggests that local reactivation of latent CMV infection is not associated with a demonstrable systemic antibody response. Inter-assay correlations were sought for each of the 10 possible combinations of pairs of tests. Significant correlations were found for most pairs of tests, with the notable exception fo those involving the early antigen test. This confirms that antibodies detected in this assay are distinct from those detected by the other 4 serological assays.

Adult↗

A comparison of complement fixation, indirect immunofluorescence for viral late antigens, and anti-complement immunofluorescence tests for the detection of cytomegalovirus specific serum antibodies.

It was shown that, on average, the titres of the sera obtained by both the anti-complement immunofluorescence (ACIF) and indirect immunofluorescence for viral late antigens (IFA-LA) procedures were approximately eight times higher than those obtained by complement fixation. There was no significant difference between the mean ACIF and IFA-LA titres, but the former method was preferred because it was not affected by non-specific staining. When 406 sera were screened for the presence or absence of antibodies, only five sera (1.2%) gave discordant results with the three tests. None of the tests could detect all of the sera that contained specific antibodies while each test detected over 98% of these sera. Thus, the increased sensitivity of the immunofluorescence procedures did not result in an appreciably increased rate of detection of cytomegalovirus seropositive sera.

Antibodies, Viral↗