[Prostacyclin metabolism disorders in the hemolytic uremia syndrome in the blood of children and members of their family].
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Biomedical subjects
Publications and source records attributed to A M Murphy.
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Superfusion of a bepridil containing normal Tyrode solution produced a concentration-dependent decrease in force development and shortening of action potential duration in isolated Purkinje strands. At a concentration close to the 50% inhibitory concentration for effects on force development and action potential duration, bepridil blocked 'slow' action potentials in potassium depolarized, isoproterenol-restored Purkinje strands. When the concentration-response relations for decreasing force development and shortening action potential duration were compared to those of nisoldipine and other calcium entry inhibitors, bepridil was the least potent. Bepridil also showed a concentration-dependent effect on the maximum rate of rise of the Purkinje fiber action potential upstroke similar to, though less potent than that of lidocaine. In addition, like lidocaine, bepridil shifted the membrane responsiveness curve of the Purkinje strands to the left. These findings indicate that bepridil produced effects that are consistent with its classification as a calcium entry inhibitor (class IV antiarrhythmic), as well as effects that are 'lidocaine-like' (class I antiarrhythmic).
When the H1N1 subtype of influenza reappeared in the Northern Hemisphere during 1977, after a 20-year absence, it behaved very differently from the H3N2 subtype still in circulation. In Sydney, we studied the incidence of both subtypes of laboratory-proven influenza type A in 287 unvaccinated volunteers whose serum antibody titres were measured before and after each winter, to facilitate the detection of subclinical as well as clinical infection. During a 1977 epidemic, the A/Victoria/3/75 strain of the H3N2 subtype attacked participants of all age groups, whereas during epidemics of 1979 and 1981, the A/USSR/90/77 and A/Brazil/11/78 strains of the H1N1 subtype attacked only subjects born after 1950. The older participants apparently possessed homologous protection, acquired as a result of exposure to H1N1 more than 20 years earlier and not dependent upon strain-specific haemagglutination inhibition antibody.
Rubella vaccination of schoolgirls aged 10-14 years started 13 years ago in Australia; the girls were vaccinated without prior assessment of their immunity. Non-pregnant seronegative women were also offered vaccination in family-planning clinics and post partum in obstetric units. Serological follow-up of 191 schoolgirls 5 years after vaccination and 56 girls 8 years after vaccination showed that all had detectable rubella antibody, whereas 24% of 239 unvaccinated young men of similar age (18-23 years) were seronegative. In 1983, 96% of 8226 pregnant women aged 12-53 years (mean 25.3 years) had detectable rubella antibody, and since 1977 there has been a striking reduction in the incidence of deafness due to congenital rubella. These results indicate that the rubella vaccination programme in Australia is having a significant impact on both the serological status of pregnant women and on the incidence of congenital infection.
An indirect solid-phase enzyme-linked immunosorbent assay (ELISA) for the determination of specific IgM and IgG antibodies to echovirus type 11 in a single dilution of serum was developed using partially purified echovirus type 11 bound to microplates. Whole serum was used for IgG antibody but prior to assaying for IgM antibody interfering IgG was removed by ion exchange chromatography. The ELISA for echovirus type 11 IgG antibody was a more sensitive, rapid, technically easier and less costly alternative to the neutralisation test. With the IgG ELISA 12 of 132 sera (10.6%) known to contain enterovirus antibodies other than echovirus type 11 were positive but it could not be determined to what extent this was due to the greater sensitivity of the ELISA or cross-reactions. The IgM ELISA was even more sensitive than the IgG ELISA with acute sera, and showed a reactivity in 4 of 36 sera (11.1%) with no detectable echovirus type 11 neutralising antibodies. Echovirus type 11 IgM antibody was detected in all sera collected after the first week of infection and up to 30 days after infection. However, it was only detected in 58% of sera collected during the first week after onset thus limiting its use for rapid diagnosis. The echovirus type 11 IgM ELISA appears to have considerable laboratory diagnostic potential when a rising antibody level cannot be demonstrated in paired sera or when virus is not cultured.
Evidence of current or past infection with hepatitis B has been studied in 809 patients attending clinics for sexually transmitted diseases in Sydney by assaying serological markers. Prevalence rates were 13.9% among male heterosexuals; 13.5% among female heterosexuals; 30.7% among female prostitutes; 64.3% among male homosexuals and 47.1% among male bisexuals. The prevalence was 80% for male homosexuals aged 36 years or more. Vaccination should be considered for persons at high risk of sexual transmission of hepatitis B, and it is the immunization of this group that is likely to have a major impact on this disease.
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We detail aspects of measles immunization programmes in several countries. Live measles vaccine has been available in Australia for 16 years, yet, in 1981, there were outbreaks of measles in the State of New South Wales (population 5 200 000) which led to 2200 admissions to hospital and five deaths. In response to complaints of "vaccine failure", a survey determined that 22.5% of children with measles seen by general practitioners and 10.3% of those admitted to hospitals had been previously immunized. There was no evidence of waning immunity, and noparticular batch of vaccine was implicated. The vaccine failures are attributed in part to failure of seroconversion in some recipients when immunized at 12 months of age as a result of interference by transplacentally acquired antibodies. As more of the susceptible population is vaccinated, there will be fewer cases of measles, but among these cases will be an increasing proportion of cases occurring in previously vaccinated individuals. The equation to calculate this expected proportion of "vaccine failures" is given. We support the measures to increase immunization compliance.
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No indigenous cases of poliomyelitis have occurred in New South Wales since 1970, and it was presumed that herd immunity was high. However, our survey of Sydney's children by the neutralization test showed that only 42% of children had antibody levels (titre 8 or higher) to all three serotypes, 30% had antibodies to two, 16% to one, and 12% had no demonstrable antibodies at all. The immune status could not be determined with confidence from the immunization history, as 48% of the children who were reported as having received four or more doses of Sabin vaccine were not fully immune. When children who had inadequate levels of antibodies were given a single dose of Sabin vaccine, 77% of them achieved adequate antibody levels to all three viruses. The Health Commission of New South Wales subsequently undertook a mass Sabin immunization campaign of primary-school children, and reviewed the recommended immunization schedule.
A high incidence of gastroenteritis in both islanders and tourists has been recorded in recent years on Norfolk Island--a popular tourist resort for Australians and New Zealanders. No bacterial cause has been found. However, electron microscopic examination of 28 faecal specimens revealed viruses associated with gastroenteritis in 21 (75%). No viruses were isolated in cell cultures. Bore water is used for drinking purposes on the island and 32 samples from 15 bores were examined for viruses by electron microscopy and culture as well as for bacterial contamination. Seven polioviruses (all type 1 vaccine strain) and adenoviruses 1 and 5 were isolated in cell cultures. In addition one rotavirus, one adenovirus and two small round viruses were detected by electron microscopy. Six of 21 samples tested showed unacceptably high levels of bacteria for drinking water. The deep ground water has apparently become contaminated with sewage effluent and is almost certainly the main cause of the high level of gastroenteritis on the island.
An enzyme-linked immunosorbent assay (ELISA) for specific IgM antibody to Coxiella burnetii was compared with the indirect immunofluorescence (FA) test in studies of 130 serum samples from 38 patients with Q fever. The IgM fractions obtained after rate zonal-density gradient ultracentrifugation of 37 serum samples from 12 patients were also studied in a complement fixation test (CF-DG). Specific IgM antibody to C burnetii was detected by all three methods in sera collected two to eight weeks after the onset of symptoms. The longest period for which specific IgM was shown to persist was 17 weeks by ELISA and FA and 10 weeks by CF-DG. The ELISA is performed with a single dilution of convalescent-phase serum and offers advantages over the subjective FA and the technically tedious CF-DG methods. The estimation of C burnetii-specific IgM by ELISA or FA is useful for the confirmation of infection when a rising titer of complement-fixing antibody cannot be demonstrated because acute-phase blood samples are not available.
Blood specimens were collected over various periods of time from 30 abattoir workers with a clinical diagnosis of Q fever. All specimens were tested for complement-fixing antibodies and for specific immunoglobulin M (IgM) globulins to phase 1 and 2 Coxiella burnetii organisms by an immunofluorescence technique. All 22 patients with increasing levels of complement-fixing antibodies were shown to have generated specific IgM globulins, as did 4 patients with high convalescent titers but from whom "acute" specimens were not collected. Four individuals who did not show increasing levels of complement-fixing antibodies did not produce measurable levels of specific IgM. All patients with Q fever gave positive specific IgM results by 2 weeks after the onset of symptoms. IgM to phase 1 antigen persisted for 27 weeks in one patient, but IgM to phase 2 antigen was not detectable beyond 17 weeks. The estimation of Q fever-specific IgM has proved useful in confirming infection when only a "convalescent" blood specimen is available.
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Twenty-two cases of pyrexial illness which occurred amongst workers in a country abattoir were investigated retrospectively for Q fever, brucellosis, and leptospirosis. In 18, the illness was shown to be Q fever. No diagnoses were established for the other four. The demonstration of circulating Q-fever-specific IgM globulin was instrumental in establishing the diagnosis in many of the cases.
Following the widespread outbreaks of oyster-associated gastroenteritis which occurred throughout Australia in 1978, several programmes were introduced to minimise the occurrence of further outbreaks. One programme included the depuration (purification) of oysters and the use of human volunteers to test-consume samples from batches of depurated oysters before their sale to the public. Oysters from the Georges River and Brisbane Waters were test-consumed from December, 1978, to August, 1979. None of the volunteers was ill after consuming Brisbane Waters oysters but 52 reported ill after eating Georges River oysters. The predominant symptoms were nausea, vomiting and diarrhoea with an average incubation period of 42 hours. Recovery was usually complete in 36-48 hours. Of the 52 illnesses reported 31 (60%) occurred in two particular weeks ending July 1st and 22nd when rates of 18.3% and 7.8% were reported. The average illness rate for the remainder of the period under study was only 1%. Norwalk virus was found in 8 of 25 (32%) stools, and antibody increases demonstrated in seven of ten paired sera, giving an overall diagnostic rate for Norwalk infection of 37.0% for these two peak periods. Heavy rain preceded these two weeks in which the illnesses occurred. No evidence of Norwalk infection was found at any other time. These studies confirmed the epidemiological findings of the major outbreak of gastroenteritis in 1978, and showed that only Georges River oysters caused Norwalk virus infections and that depuration as carried out in 1979 was not entirely satisfactory.
Forty newborn babies who were shown to be excreting rotaviruses within a few days of birth were tested daily for one month. Most were found to excrete virus for only a short period of time. In 48% of babies, virus was found on one day only, in 25% it was present for two days, and in 10% for three days. Most of these infections did not appear to confer lasting immunity. Only 21% of young children who excreted virus as neonates had detectable circulating complement-fixing antibodies when eight to eighteen months old. A survey of newborn babies showed that 89% of babies possessed the antibody, but, by the age of four to six months, the antibody was present only in 7%. This supports the view that infected neonates fail to develop circulating complement-fixing antibodies. Infection rates did not differ significantly between breast-fed and bottle-fed babies. Likewise, maternal antibody levels could not be shown to have any effect on infection. No rotavirus particles were found in breast milk.
Following widespread outbreaks of oyster-associated gastroenteritis in Australia during 1978 in which Norwalk virus was implicated as the causative agent, collaborative studies were undertaken between laboratories in Australia and the United States to confirm the etiology. Immune electron microscopy (IEM) techniques were used in Australia and radioimmunoassay (RIA) methods in the United States. Norwalk virus was detected by IEM in seven of 15 faecal samples, and four were positive by RIA. A much better correlation was found with antibody determinations. Both methods demonstrated significant increases in antibody to Norwalk virus in 22 of 30 sets (73%) of "acute" and "convalescent" sera, confirming that Norwalk virus was responsible for the majority of cases. It is significant that the RIA serology was determined using Norwalk antigen originating in the United States and the IEM serology was determined using 27--30-nm particles originating in Australia.