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Biomedical subjects

J M Forrest

Publications and source records attributed to J M Forrest.

At least 19 recordsLinked to original sources

Measles control in Australia. Report of the Measles Control in Australia Workshop, 5 November 1997.

The proceedings of the Measles Control in Australia Workshop held on 5 November 1998 are presented in this report. Prompted by the possibility of a global elimination campaign in the near future the Workshop considered the factors involved in elimination of measles from Australia. Epidemiology, surveillance, laboratory diagnosis methods, mathematical modelling, and the cost and logistics were all addressed. Mass vaccination for all 2-18 year olds, and a routine 2-dose regimen with scheduled doses at 12 months and school entry were recommended. Intensified surveillance, based on a sensitive case definition and laboratory confirmation (measles specific IgM) of suspected cases was identified as a crucial component of the campaign. The continuation of high vaccination coverage for each of the two doses would be essential to maintain elimination once established.

Adolescent

Varicella-zoster virus infection in Australia.

OBJECTIVE: To determine the epidemiology of varicella-zoster virus (VZV) infection in Australia using currently available data sources. DESIGN: Analysis of national death data (23 years), congenital and neonatal cases (one year) and attendances at sentinel general practices (two years); hospital admissions in NSW and SA (six years); serological studies in 1995 involving antenatal clinics in Sydney and Brisbane and child-care centre staff and refugees in Sydney; and case-ascertainment in 1995 in South Western Sydney among public hospital staff, child-care centre staff and the community. RESULTS: In Australia, there have been an average of 3.5 deaths from chickenpox (mostly children) and 11 from herpes zoster (mostly older people) each year since 1980. The crude death rate for chickenpox has declined (p > 0.05). In 1995, there were 14 cases of neonatal and two of congenital varicella. Average annual admission rates for NSW and SA showed 1,200 hospital bed-days used for chickenpox, more than 20% with complications, and more than 7,300 bed days for zoster; annually more than 880 in-patient admissions were complicated by VZV. Most people encounter the virus in their first 15 years, but some remain susceptible into their 20s; 25% of cases and 37% of hospital admissions for chickenpox occur in people > or = 15 years of age. CONCLUSION: VZV infection involves people of all ages. It causes substantial morbidity and mortality, particularly at the extremes of life. The death rate from chickenpox but not zoster has fallen since the introduction of acyclovir in the 1980s. Surveillance of VZV infection must be given priority once vaccines become available, to monitor changes in morbidity and mortality.

Adolescent

Update on immunization.

By 1995, measles, mumps, and rubella were eliminated from Finland, acellular vaccines for pertussis were showing great promise, and the global eradication of poliomyelitis by the year 2000 looked possible. The meningococcus was replacing Haemophilus influenzae type b as the main cause of childhood meningitis, and 75 countries were vaccinating their children against hepatitis B. The United States recommended varicella vaccination for children, effective vaccines were available for hepatitis A, and new vaccines for rotavirus and cholera were being tested; malaria and HIV offer a continuing challenge.

Chickenpox

A pilot study of a computerized assessment (AGE-PC) for the elderly in general practice.

A pilot project was undertaken in Liverpool UK, to investigate whether data useful for both general practice and public health purposes could be collected by primary care personnel using a computerized semi-structured interview (AGE-PC) for assessment of patients aged 75 and over. A high degree of variation between practices was found in the proportion of elderly assessed with AGE-PC largely related to motivation to undertake assessments and methods employed to approach patients. Considerable differences between and within practices were evident in staff attitudes to the need for detailed formal assessments and the use of computers. Several aspects of the AGE-PC package itself were identified as requiring modification including streamlining data transfer methods, adding facilities for analysis and giving users a degree of choice over content of the assessment. This technique does offer a potentially efficient means of collecting very detailed standardized data for intra- or inter-practice analysis while at the same time generating a comprehensive report for individual patients. However, in the context of the over-75 assessments it was too time-consuming. Possible future strategies are discussed such as using an initial screening stage with a self-report questionnaire to reduce numbers needing full assessment and the use of the package for the community care assessments. The pilot project highlighted some of the potential advantages and disadvantages of collecting data from primary health care for public health purposes.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Interaction of 68-kDa TAR RNA-binding protein and other cellular proteins with prion protein-RNA stem-loop.

The RNA stem-loop structure of the trans-activating region TAR sequence of human immunodeficiency virus-1 mRNA is the binding site for a number of host cell proteins. A virtually identical set of proteins from HeLa nuclear extracts was found to bind to the predicted RNA hairpin element of prion protein (PrP) mRNA, as demonstrated in UV cross-linking/RNase protection and Northwestern assays. We show that the cellular TAR loop-binding protein, p68, is among those proteins which associate with PrP RNA. Competition experiments with various TAR RNA mutants revealed that binding of partially purified p68 to PrP RNA stem-loop occurs sequence-specifically. The 100-kDa 2-5A synthetase which is involved in the cellular antiviral defense was able to bind to PrP mRNA stem-loop in Northwestern blots with cytosolic proteins from HeLa cells treated with interferon. However, the PrP RNA failed to activate this enzyme in vitro, in contrast to TAR RNA.

2',5'-Oligoadenylate Synthetase

Cytoprotective effect of NMDA receptor antagonists on prion protein (PrionSc)-induced toxicity in rat cortical cell cultures.

Rat cortical cells were incubated with the Scrapie prion protein, PrionSc. At concentrations of 3 ng/ml of PrionSc and higher, the viability of the cells decreased significantly after a 12-h incubation period. Simultaneously, the degree of DNA fragmentation increased. In control experiments with antibodies against PrionSc, PrionSc lost its deleterious effect on neurons. PrionSc did not affect the viability of astrocytes. Drugs known to block NMDA receptor channels, such as memantine (1-amino-3,5-dimethyl-adamantane) (Mem), its analogue 1-N-methylamino-3,5-dimethyl-adamantane as well as (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) prevented the effect of PrionSc. Production of PrionSc in the Scrapie prion-infected subclone of N2 a cells (ScN2 a cells) was not affected by memantine. We conclude that antagonists of the NMDA receptor-channel complex (i) abolish the PrionSc-induced neuronal injury in vitro, and (ii) display no influence on the synthesis and/or the processing of PrionSc.

Animals

Human immunodeficiency virus: novel enzyme-linked immunoassays for quantitation of envelope glycoprotein 120.

Two novel enzyme-linked immunoassays (ELISA) for the quantitation of human immunodeficiency virus type 1 (HIV-1) coded glycoprotein with an Mr 120 (gp120) are described. These are based on the highly specific interaction between gp120 and the mannose-specific lectins from Narcissus pseudonarcissus (NPL) and Galanthus nivalis (GNL). Two systems were developed: (1) an HIV-protein ELISA using HIV-protein (also containing HIV-gp120) for the solid phase and NPL as a detector and (2) a lectin-ELISA using the NPL bound to the solid phase and GNL as detector. The HIV-protein ELISA was validated for quantitation of gp120 within the range 3 to 600 ng/ml; the lectin-ELISA for concentrations between 0.6 and 20000 ng gp120/ml. Serum components did not interfere with the binding of gp120 to the lectins. The ELISAs were used for the quantitation of gp120 in HIV-infected CEM cells in vitro. It was found that gp120 appeared in the medium earlier after infection than HIV-p24 and reverse transcriptase, suggesting that gp120 is released as free glycoprotein. Moreover, the ELISAs were also applied successfully for the detection of compounds that bind to gp120 and for the identification of antibodies directed against the highly pathogenic mannan portion of gp120. These ELISAs are considered to be suitable also for the detection of gp120 in the serum of HIV-infected individuals.

Animals

Sulphoevernan, a polyanionic polysaccharide, and the narcissus lectin potently inhibit human immunodeficiency virus infection by binding to viral envelope protein.

Sulphoevernan is a sulphated alpha-1----3, 1----4 polyglucan (Mr 20,000) with a helical structure. This compound effectively inhibits both human immunodeficiency virus type 1 (HIV-1) and type 2 infection of cells in vitro at concentrations around 0.5 micrograms/ml. Moreover, the compound completely inhibits HIV-1-induced syncytium formation at a concentration of 1 microgram/ml. Competition experiments with 35S-labelled sulphoevernan revealed that the mannose-specific lectin from Narcissus pseudonarcissus prevented binding of sulphoevernan to HIV-1, whereas the antibody OKT4A did not reduce the amount of sulphoevernan bound to MT-2 cells. These data indicate that the non-cytotoxic polymer sulphoevernan binds to the virus rather than to the host cell. In vivo studies, using Rauscher leukaemia virus in NMRI mice, revealed that, at a daily dose of 20 mg/kg, the animals were protected against virus-induced increases in spleen weight. From these in vitro and in vivo data we conclude that sulphoevernan has potential in the treatment of acquired immunodeficiency syndrome.

Antiviral Agents

Continuing education: a survey among general practitioners.

A survey of perceptions of continuing education--content, methods and current provision--was undertaken among all established general practitioners in one health region of the UK using a postal questionnaire. Interviews were conducted with a small random sample of respondents and with a larger sample of non-respondents to the questionnaire. Data from the questionnaire and interviews demonstrated overall a wide diversity of content and methods of continuing education perceived as appropriate, with duration of experience and involvement in undergraduate teaching or postgraduate training as significant determinants. The findings are used to review, critically, current provision of continuing education for general practice and to suggest ways in which future provision might reflect the range of educational need perceived by doctors.

Age Factors

Congenital limb reduction deformities and use of oral contraceptives.

A study of congenital limb deficiencies in two Australian states indicated that use of an oral contraceptive during pregnancy by the mother was associated with an increased risk of limb defect in the child. The study included mothers of 155 children born with absence or reduction of the major long bones during a 12-year period from 1970 onward; 274 mothers with births of normal infants, matched for date of birth and area of residence, made up the control group. Compared with control infants, the case infants were more likely to have been conceived while the mother was using an oral contraceptive, especially when the deformity was a transverse or amputation type. It is too early in our state of knowledge of teratogenic mechanisms to exclude the possible existence of a biologic mechanism that would explain this statistical association.

Abnormalities, Drug-Induced

Gestational diabetes--infant malformations and subsequent maternal glucose tolerance.

The frequency of abnormal glucose tolerance in the first 12 months after gestational diabetes was found to be 33.3%, which is much higher than previously accepted. Women with gestational diabetes (Group 1 = 54 requiring insulin, Group 2 = 32 treated with diet alone) attending a metropolitan teaching hospital over a 3 1/2 year period were followed-up after delivery to determine their subsequent glucose tolerance. Of 86 seen 3 months after delivery, 2 had developed insulin-dependent diabetes mellitus (IDDM) and 2 noninsulin dependent diabetes mellitus (NIDDM), diagnosed by glucose tolerance testing. Another 38 returned for follow-up glucose tolerance testing at 12 months; of these 3 had impaired glucose tolerance (IGT), 7 had NIDDM, and one who had had NIDDM at 3 months now showed IGT after 9 months dietary treatment. Thus, 12 months after delivery, the cumulative prevalence of abnormal glucose tolerance was 14/42 (33.3%), 10 of the 42 being frankly diabetic (26%). Of the remaining 44 patients, 21 have not yet reached 12 months or were pregnant again, and 23 did not attend for glucose tolerance testing. Although the trend was for gestational diabetes mellitus (GDM) to recur earlier and more severely in subsequent pregnancies, in 3 instances the diabetes did not recur. Major congenital malformations occurred in 4 of the 86 babies (4.7%); minor malformations were found in a further 13 (15%) with no difference in frequency between Group 1 and Group 2.

Adult

The compliance of diabetic patients: relationship between subjective assessment by physicians and objective measurement of patient performance.

During a survey period of 9 months, diabetic patients attending an outpatient clinic were asked routinely by the nursing staff to produce their home urine/glucose monitoring charts and diet charts. If they could not do so, the importance of bringing these charts was explained and they were instructed to bring their charts at subsequent visits. In addition, the individual responses of 109 consecutive patients were monitored as index cases. The physicians of these 109 patients were asked to grade each patient according to their estimate of the patient's compliance. This subjective rating was correlated with the actual performance of the patients in bringing charts. During the survey the overall number of patients attending the clinic who brought urine/blood charts increased from 31% to 59%. The corresponding figures for diet charts were 6% and 21%. Before intervention, the group rated "high compliance" was more likely than the "low compliance" rated group to bring urine/glucose charts. However, after adjustment for this baseline difference the subsequent performances of the high and low rated groups were comparable. These two groups of patients also performed similarly with respect to diet charts. It is concluded that patients judged subjectively to have poor compliance were able to modify their behaviour similarly to those assessed as having good compliance.

Adult

Rubella vaccination in Australia: 1. A five-year follow-up of vaccinated schoolgirls.

Schoolgirl rubella vaccination commenced in New South Wales in 1971. Serological follow up of 242 girls, four to five years after vaccination, showed that 9% of girls had missed the vaccination programme. Only 5% of vaccinees were still susceptible to rubella in comparison with 27% of unvaccinated male controls. The efficacy of the programme is thus well demonstrated. Screening for vaccine failures at the time of prescribing contraceptives is suggested as a means of detecting schoolgirl vaccine failures. It is noted that the first cohort of schoolgirl vaccinees has not yet reached the peak childbearing age range.

Adolescent

Rubella vaccination in Australia: 2. Experience with the RA27/3 rubella vaccine and results of a double-blind trial in schoolgirls.

RA27/3 rubella vaccine (Almevax) was used for the first time in Australia. The seroconversion rate was similar to that seen with Cendehill vaccine (Cedevax), but there were fewer subjects with low antibody titres after Almevax vaccine. Although Almevax vaccine was associated with a significantly higher incidence of sore throat, rash and joint involvement in seronegative adults, the incidence of side effects in a double-blind trial in schoolgirls was similar for the two vaccines, and the morbidity was low in both groups. Almevax vaccination successfully boosted low antibody titres in 11 of 14 women who had previously responded poorly to Cendevax vaccination. It would be difficult to differentiate the better vaccine for the schoolgirl programme. In some clinical situations, however, one vaccine has advantages over the other.

Adolescent

Rubella infection and diabetes mellitus.

The incidence of diabetes mellitus was increased in patients with congenital rubella. Experimental congenital rubella infection in rabbits caused histological changes in the beta-cells of the pancreatic islets similar to those found in mice made diabetic by the M variant of the encephalomyocarditis virus. It is concluded that the diabetes seen in congenital rubella is due to viral infection of the pancreatic islet cells.

Adult