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Biomedical subjects

P N Goldwater

Publications and source records attributed to P N Goldwater.

At least 19 recordsLinked to original sources
PubMed2003

Sudden infant death syndrome: a critical review of approaches to research.

This review explores the various research approaches taken attempting to solve the problem of SIDS. It would appear that major clues provided by pathological findings have been largely overlooked and as a consequence much effort, time, and money has been wasted on projects that satisfy only sub-specialty and political needs. Close examination of the pathological clues would provide better insights into the mechanisms underlying this enigmatic and heartbreaking problem.

Bacterial Toxins↗
PubMed2001

Bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease: implications for Australia.

The bovine spongiform encephalopathy (BSE) epizootic developed in the United Kingdom in the mid-1980s. Feeding practices in the cattle industry amplified the causative prion, and meat contaminated with BSE entered the market. Human consumption of prion-contaminated meat led to the new zoonosis--variant Creutzfeldt-Jakob disease (vCJD). The UK BSE Inquiry published its report in October 2000; while praising policy decisions, it also documented failures in the execution of these policies, specifically delays and lack of rigour. Australia is in an excellent position to maintain its BSE- and scrapie-free status, but widespread active surveillance of neural and non-neural tissue from all species of farmed quadrupeds is needed.

Animals↗
PubMed2001

SIDS: more facts and controversies.

A more robust theory of the causation of sudden infant death syndrome (SIDS) is needed. The asphyxial theory of SIDS, which encompasses the prone sleeping position, relies on contradictory pathological evidence and fails to explain infants with SIDS who are found in the supine or lateral position. Many of the risk factors for SIDS point to an infective cause. The relative risks of these infection-related factors differ from study to study, as does the relative risk of prone sleeping position. I present the case for an infection model for SIDS causation, which has largely been neglected by mainstream SIDS researchers.

Endotoxemia↗
PubMed2001

Rotavirus encephalopathy: pathogenesis reviewed.

Two cases of rotavirus gastroenteritis associated with neurological involvement, one with encephalitis (defined by abnormal neurological signs, cerebrospinal fluid (CSF) pleocytosis and detection of rotavirus genomic nucleic acid in the CSF) and one with a non-inflammatory encephalopathy (defined by abnormal neurological signs, an entirely normal CSF and detection of rotavirus genomic nucleic acid in the CSF), are presented and used as a basis to review and explore potential pathogenetic mechanisms, including direct viral replication within neurons and indirect effects of the newly described rotavirus 'enterotoxin'.

Acyclovir↗
PubMed2000

Escherichia coli 'O' group serology of a haemolytic uraemic syndrome (HUS) epidemic.

This is the first comprehensive serological analysis of a haemolytic uraemic syndrome (HUS) outbreak. A wide range of 'O' group Escherichia coli antibody responses in patients and controls was examined. The study provides a unique insight into the epidemiology of such epidemics, points a way to the most appropriate investigation of these and indicates possible answers to a number of issues related to severity of disease. In order to be able to test for a wide variety of E. coli 'O' antigens, a microagglutination assay was used to examine E. coli 'O' group serological responses of 22 children admitted to hospital with HUS and 14 contemporaneous age-matched controls. A total of 51 'O' serogroup strains were used. These included 'O' groups reported to be associated with cases of HUS, with 6 isolates from patients associated with the Adelaide outbreak (O26, O111, O123 and O157), environmental Verocytotoxigenic/Shiga-toxin producing Escherichia coli (VTEC/STEC) strains and common human commensal strains. Sixteen clinically confirmed HUS cases (72.7%) of 22 seroconverted to 1 or more serogroups of which 11 (50%) seroconverted to O111 (the serogroup isolated from 16 patients). In addition, 11 (50%) and 10 (45.5%) developed antibody to O137 and O145, respectively, although no stool isolates of these serogroups were made. Seventeen (77.3%) of 22 HUS patients had antibody to serogroup O157, with 11 (50%) seroconversions, however, O157:H- was isolated from only 2 of these. Overall, titres ranged from 100 to 6400, some of the highest in 3 patients were against O157, whose faeces yielded only Enterohaemorrhagic E. coli (EHEC) O111, and only 1 developed O111 antibody. Mixed infection was demonstrated serologically by microagglutination (confirmed by Western blot) and was consistent with the findings of multiple serogroups of VTEC found in the mettwurst incriminated as the source, and suggests further strains (not found in the source or in patients' faeces) were probably also involved. In HUS associated with EHEC infection, multiple strain infection may be the rule rather than the exception. A relationship with clinical severity deserves further investigation. Non-O157 EHEC (in addition to O157) should be sought in all future outbreaks of EHEC disease.

Child↗
PubMed2000

Association between rotavirus infection and pancreatic islet autoimmunity in children at risk of developing type 1 diabetes.

Pancreatic islet autoimmunity leading to type 1 diabetes could be triggered by viruses in genetically susceptible individuals. Rotavirus (RV), the most common cause of childhood gastroenteritis, contains peptide sequences highly similar to T-cell epitopes in the islet autoantigens GAD and tyrosine phosphatase IA-2 (IA-2), suggesting T-cells to RV could trigger islet autoimmunity by molecular mimicry. We therefore sought an association between RV infection and islet autoantibody markers in children at risk for diabetes who were followed from birth. There was a specific and highly significant association between RV seroconversion and increases in any of these antibodies: 86% of antibodies to IA-2, 62% to insulin, and 50% to GAD first appeared or increased with increases in RV IgG or IgA. RV infection may therefore trigger or exacerbate islet autoimmunity in genetically susceptible children.

Antigens, Viral↗
PubMed1998

An unusual case of microangiopathic haemolytic anaemia associated with enterohaemorrhagic Escherichia coli O113:H21 infection, a verocytotoxin-2/shiga toxin-2 producing serotype.

A case of microangiopathic haemolytic anaemia and thrombocytopaenia in a 79-year-old woman is presented. The case is unusual in that diarrhoeal symptoms were brief and symptoms of anaemia caused her to re-present to hospital 6 days after the diarrhoea had ceased. Enterohaemorrhagic Escherichia coli O113:H21 producing shiga toxin-2 was isolated from a faecal specimen. This serotype has been reported only a few times to be associated with serious disease. However, it is amongst the 20 most common serotypes carried in cattle and found in beef. This case also illustrates the importance of using shiga-toxin gene detection in faecal cultures (as opposed to cultural methods for detection of the O157:H7 serotype) as the recommended investigation of human disease for accurate epidemiology and attribution of cause.

Aged↗
PubMed1998

New perspectives on the role of Escherichia coli O157:H7 and other enterohaemorrhagic E. coli serotypes in human disease.

This review compares the rates of detection of non-O157:H7 enterohaemorrhagic Escherichia coli (EHEC) with EHEC O157:H7 in outbreaks and sporadic cases of human disease by analysing Australian data and the world literature. Numerous outbreaks of disease have been attributed to EHEC O157:H7. In many studies, isolation rates of this organism have been low and attempts to seek other EHEC have not been made. Ease of isolation and identification of the O157:H7 serotype may have given the impression that this serotype was the sole organism responsible for the outbreaks. Careful review and analysis shows that serotypes other than O157:H7 also play an important role in human disease. Evidence is presented from several overseas outbreaks described in the literature, as well as from investigations of the Adelaide O111:H- outbreak, that suggests an association between severity of disease and multiple infecting serotypes. While not diminishing the role of the O157:H7/H- clone, this review indicates that other serotypes can be responsible for outbreaks as well as cases of sporadic human disease. The current focus on O157:H7 has major implications in terms of diagnosis, the food industry and human health.

Australia↗
PubMed1997

Randomized, comparative trial of 20 micrograms vs 40 micrograms Engerix B vaccine in hepatitis B vaccine non-responders.

Fifty-two adults who had previously received 4 x 20 micrograms doses of hepatitis B [Engerix-B] vaccine (appropriately administered into the deltoid muscle) and who had failed to develop detectable anti-HBs were randomized to receive a fifth dose of Engerix-B (either 20 micrograms or 40 micrograms) intramuscularly (deltoid). The participants were blinded as to the contents of the syringe. Anti-HBs was tested (by EIA) 3 months after the injection. Anti-HBs results from 45 non-responders were evaluable. Seven vaccinees were excluded; four of these on the basis of failure to have follow-up blood collected and three who were found to be anti-HBc positive (one HBsAg positive). Twelve of 22 (54.5%) of those receiving 20 micrograms of HB vaccine developed anti-HBs, whereas 10 of 23 (43.5%) who received 40 micrograms developed anti-HBs, showing no significant difference between the regimens. The mean geometric titres were 93 +/- 50 and 86 +/- 51 IU l-1, respectively. Vaccinee groups were well matched for age, sex and body mass index and the interval between injection and bleeding. Side-effects in those receiving the double (40 micrograms) dose were no different from those receiving the normal (20 micrograms) adult dose. On the basis of this study, a fifth dose of vaccine in non-responsive vaccinees is recommended. No significant advantage of 40 micrograms over 20 micrograms of vaccine was observed. Whilst smoking and obesity were common in this cohort of non-responders and probably contributed to the individuals primary non-responsive state, these factors had no unfavourable effect on response to a fifth dose of vaccine.

Adolescent↗
PubMed1996

Routine microbiological testing in sudden and unexpected infant death.

OBJECTIVE: To evaluate the significance of microbiological test results in a series of infants who had died suddenly and unexpectedly. METHODOLOGY: Following a review of all cases of sudden natural death in infants presenting to the Adelaide Children's Hospital (ACH) division of the Women's and Children's Hospital (WCH) over the 10 year period between 1983 and 1992, specific evaluation of microbiological test results was undertaken. RESULTS: There were 329 cases of sudden infant death syndrome (SIDS) and 23 cases in which sudden infant death was either attributed to other conditions or was unclassifiable. Positive microbiological results were recorded in the majority of cases, most being considered to be due to postmortem overgrowth or to contamination at autopsy. Of the remaining cases, microbiological results were essential to the establishment of the diagnosis in three cases, and were a useful adjunct to the diagnosis in a further six cases. CONCLUSIONS: Routine microbiological testing in cases presenting as SIDS did not reveal occult sepsis in most instances. Such testing did, however, add support to the diagnosis of SIDS where no pathogens were isolated and, if not undertaken, would have resulted in a small percentage of cases of sudden infant death due to infections remaining undiagnosed.

Autopsy↗
PubMed1995

Effect of cefotaxime or ceftriaxone treatment on nasopharyngeal Haemophilus influenzae type b colonization in children.

The effects of cefotaxime and ceftriaxone treatment on nasopharyngeal carriage of Haemophilus influenzae type b (Hib) were prospectively studied with 53 children with invasive Hib disease. Nasopharyngeal aspirates were monitored during therapy. Hib was eliminated within 2 days in 92% of patients and was eliminated in all patients after the third day of antibiotic treatment.

Cefotaxime↗
PubMed1995

Immunoglobulin M capture immunoassay in investigation of coxsackievirus B5 and B6 outbreaks in South Australia.

An immunoglobulin M (IgM) capture enzyme immunoassay was used to detect major overlapping outbreaks of disease in South Australia caused by coxsackieviruses B5 (CBV-5) and B6 (CBV-6). CBV-5-specific IgM was detected in patients presenting in spring 1992 with acute febrile illnesses, rash, severe acute respiratory disease, meningitis, myocarditis and/or pericarditis, while tests for other viruses were negative. CBV-5 was isolated from an early case. In December 1992 it was noted that CBV-6 had replaced CBV-5 as the major cause of disease. The CBV-6 epidemic continued until April 1993. Serum samples from 495 patients (276 inpatients) were submitted for testing. CBV-6 infection was associated with lower respiratory tract infection and persistent cough. This study demonstrated success of the IgM enzyme immunoassay and the need for diagnostic virology laboratories to look for CBV-6 infection in addition to the other five CBVs.

Adolescent↗
PubMed1994

Randomized comparative trial of interferon-alpha versus placebo in hepatitis B vaccine non-responders and hyporesponders.

Adults who had received 4 x 20 micrograms doses of hepatitis B (Engerix-B) vaccine (appropriately administered) and who had failed to develop detectable anti-HBs or who had had a minimal response (< 10 IU l-1) were randomized to receive either a fifth dose of Engerix-B (20 micrograms) plus 1 million units of interferon-alpha or a fifth dose of vaccine plus saline placebo intramuscularly (deltoid). Both vaccine and test material were given together in one syringe and participants were blind as to the syringe contents. Anti-HBs was tested (by enzyme immunoassay) one to three months following the injection. Anti-HBs results from the 150 non-responders (NR) and the 26 hyporesponders (HR) are reported. Of NRs receiving a fifth dose plus placebo, 41% developed anti-HBs, whilst 53% of those receiving interferon-alpha developed anti-HBs. The response rates did not differ significantly. Of HRs receiving vaccine plus placebo, 70% showed an increase in their anti-HBs titre, while 87.5% of those receiving interferon-alpha with vaccine had titre rises. Vaccinee groups were well matched for age, sex and body mass index and the interval between injection and venepuncture. Side-effects from interferon-alpha were of short duration and were tolerated by vaccines seeking protection from hepatitis B infection. On the basis of this study, a fifth dose of vaccine in non- and hyporesponsive vaccinees is recommended. Interferon-alpha was of unproven value but it may increase the likelihood of seroconversion in NRs and its use could be considered in subjects at continued high risk of contracting hepatitis B.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗