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Biomedical subjects

Peter McIntyre

Publications and source records attributed to Peter McIntyre.

At least 37 records · Page 2Linked to original sources
PubMed2004

Vaccine preventable diseases and vaccination coverage in Aboriginal and Torres Strait Islander people, Australia, 1999 to 2002.

This report complements the Vaccine Preventable Diseases and Vaccination Coverage reports produced biannually since 2000 by the National Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases in association with the Australian Institute of Health and Welfare. It integrates the available sources of routinely collected data relevant to the current status of vaccine preventable diseases and vaccine coverage in Aboriginal and Torres Strait Islander people in Australia. It aims to better inform Indigenous communities, Indigenous health care providers and planners of immunisation services of the current status and future needs for vaccine prevention in Indigenous people. The data presented here demonstrate that vaccination programs have had a significant impact on the health of Aboriginal and Torres Strait Islander people. Several areas are highlighted for further development of vaccination policy recommendations, in particular high rates of preventable hepatitis A and B, influenza and pneumococcal disease. Areas where more research is needed include means to more accurately monitor vaccination status, the applicability of meningococcal serogroup B vaccines when available, and effective ways of increasing vaccination coverage and timeliness of vaccination. Such issues need to be considered and implemented in full cooperation with Aboriginal and Torres Strait Islander people.

Bacterial Vaccines↗
PubMed2004

Surveillance of adverse events following immunisation: Australia 2002 to 2003.

Reports of suspected adverse events following immunisation (AEFI) are reviewed by the Adverse Drug Reactions Advisory Committee and collated in a central database. We analysed AEFI records for vaccines administered during October 2002 to December 2003, and assessed AEFI reporting trends for 2000 to 2003. AEFI reporting rates were calculated using denominator data from the Australian Childhood Immunisation Register and the annual national influenza vaccination coverage survey. A total of 1,744 AEFI records were analysed for October 2002 to December 2003. The majority described non-serious events; 9 per cent (n=149) described AEFIs defined as 'serious'. Four deaths were reported but none were causally related to immunisation. Dose-based AEFI reporting rates were 2.1 per 100,000 doses of influenza vaccine for adults aged 40 years or over and 19.8 per 100,000 doses of scheduled vaccines for children aged <7 years. The most frequently reported individual AEFI was injection site reaction in children after a fourth or fifth dose of an acellular pertussis-containing vaccine (54 and 98 reports per 100,000 doses respectively). The most frequently suspected vaccine was meningococcal C conjugate vaccine (34% of reports-mostly injection site reactions, gastrointestinal symptoms and headaches). The average annual reporting rate was 7.0 per 100,000 population, the highest to date. The increase in the AEFI reporting rate was due to a greater number of children becoming eligible to receive a fourth or fifth consecutive dose of acellular pertussis vaccine and the introduction of the meningococcal C vaccination program in January 2003 for those aged 1-19 years. The low reporting rate of serious AEFIs demonstrates the high level of safety of vaccines in Australia.

Adolescent↗
PubMed2004

Are general practice registrars prepared for immunisation? A cross sectional survey.

OBJECTIVE: To describe undergraduate formal training on immunisation as remembered by general practice registrars and its perceived helpfulness. SETTING AND METHODS: Self completed questionnaire by all general practice registrars in advanced general practice terms (second 6 months of general practice) in New South Wales during 2002. RESULTS: Formal undergraduate training in immunisation was reported by 68% (84/123) of respondents. The 20% who remembered formal practical training were significantly more likely to rate it as helpful (OR: 1.7 p<0.05). Only 33% recalled a practical session offered by one university during an undergraduate paediatrics rotation. The most frequent training request was for practical experience, and the most commonly used print resource was the Australian Immunisation Handbook. DISCUSSION: General practice registrar access to a training session on practical immunisation techniques and childhood immunisation before commencing the basic general practice term might be helpful. Registrars should automatically receive a copy of the Australian Immunisation Handbook which might address perceived education needs.

Attitude of Health Personnel↗
PubMed2003

Public opponents of vaccination: a case study.

Opposition to mass childhood vaccination is a world-wide phenomenon, particularly in industrialised countries. Unfounded claims about vaccination are perpetuated by parental lobby groups and individual spokespeople, some of whom have a medical or scientific background. This article focuses on one such spokesperson who has achieved particular notoriety. Dr. Viera Scheibner is a retired micropalaeontologist, without any formal training in health-related sciences, who tours the world claiming that vaccines are ineffective and dangerous and lead to a host of ills such as cancer and asthma. Professionals in public health or the clinical arena are from time to time called upon to publicly respond to her, or similar, claims disseminated during tours of Europe, North America or Australasia and in books and articles. Health professionals have expressed at how such spokespersons misrepresent the evidence on vaccine safety, resulting in the potential to undermine public confidence in immunisation. Media coverage, or proposed coverage, particularly of her more extreme claims, often makes health professionals engaged in immunisation feel obliged to respond. This paper describes Viera Scheibner's approach, which follows a repetitious path and is representative of that taken by other public opponents of immunisation. We conclude by suggesting how health professionals might respond in the public arena.

Attitude to Health↗
PubMed2003

ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures.

Mammals detect temperature with specialized neurons in the peripheral nervous system. Four TRPV-class channels have been implicated in sensing heat, and one TRPM-class channel in sensing cold. The combined range of temperatures that activate these channels covers a majority of the relevant physiological spectrum sensed by most mammals, with a significant gap in the noxious cold range. Here, we describe the characterization of ANKTM1, a cold-activated channel with a lower activation temperature compared to the cold and menthol receptor, TRPM8. ANKTM1 is a distant family member of TRP channels with very little amino acid similarity to TRPM8. It is found in a subset of nociceptive sensory neurons where it is coexpressed with TRPV1/VR1 (the capsaicin/heat receptor) but not TRPM8. Consistent with the expression of ANKTM1, we identify noxious cold-sensitive sensory neurons that also respond to capsaicin but not to menthol.

Amino Acid Sequence↗
PubMed2003

The VR1 antagonist capsazepine reverses mechanical hyperalgesia in models of inflammatory and neuropathic pain.

Vanilloid receptor type 1 (VR1) (TRPV1) is a ligand-gated ion channel expressed on sensory nerves that responds to noxious heat, protons, and chemical stimuli such as capsaicin. Herein, we have examined the activity of the VR1 antagonist capsazepine in models of inflammatory and neuropathic pain in the rat, mouse, and guinea pig. In naïve animals, subcutaneous administration of capsazepine (10-100 mg/kg s.c.) did not affect withdrawal thresholds to noxious thermal or mechanical stimuli. However, pretreatment with capsazepine prevented the development of mechanical hyperalgesia induced by intraplantar injection of capsaicin, with a similar potency in all three species. Capsazepine (up to 100 mg/kg s.c.) did not affect mechanical hyperalgesia in the Freund's complete adjuvant (FCA)-inflamed hind paw of the rat or mouse. Strikingly, capsazepine (3-30 mg/kg s.c.) produced up to 44% reversal of FCA-induced mechanical hyperalgesia in the guinea pig. Capsazepine also produced significant reversal of carageenan-induced thermal hyperalgesia in the guinea pig at 30 mg/kg s.c., but was ineffective in the rat. Similarly, in the partial sciatic nerve ligation model of neuropathic pain, capsazepine was surprisingly effective in the guinea pig, producing up to 80% reversal of mechanical hyperalgesia (1-30 mg/kg s.c.) but had no effect in the rat or mouse. These data show that VR1 antagonists have antihyperalgesic activity in animal models of chronic inflammatory and neuropathic pain, and illustrate species differences in the in vivo pharmacology of VR1 that correlate with differences in pharmacology previously seen in vitro.

Algorithms↗
PubMed2003

Geographic classification of extra virgin olive oils from the eastern Mediterranean by chemometric analysis of visible and near-infrared spectroscopic data.

Visible and near-infrared reflectance spectra have been examined for their ability to classify extra virgin olive oils from the eastern Mediterranean on the basis of their geographic origin. Classification strategies investigated were partial least-squares regression, factorial discriminant analysis, and k-nearest neighbors analysis. Discriminant models were developed and evaluated using spectral data in the visible (400-750 nm), near-infrared (1100-2498 nm), and combined (400-2498 nm) wavelength ranges. A variety of data pretreatments was applied. Best results were obtained using factorial discriminant analysis on raw spectral data over the combined wavelength range; a correct classification rate of 93.9% was obtained on a prediction sample set. Though the overall sample set was limited in numbers, these results demonstrate the potential of near-infrared spectroscopy to classify extra virgin olive oils on the basis of their geographic origin.

Algorithms↗
PubMed2003

Pneumococcal disease in Australia: current status and future challenges. A report of the workshop held at the National Centre for Immunisation Research and Surveillance, 8-9 November, 2002.

In relation to surveillance, the predominant issue discussed was universal versus sentinel enhanced surveillance of IPD. In northern Australia, it will be important for enhanced surveillance to continue and to be as complete as possible. There are a number of reasons for this. First, the high incidence and high serotype diversity of IPD in Indigenous children in these areas has prompted the recommendation for boosters with 23vPPV to increase serotype coverage. This makes high quality, comprehensive surveillance essential for national policy. It is also important internationally as such as vaccine program has not been implemented anywhere else but is potentially applicable to other comparable populations. Secondly, the small absolute numbers of cases require data to be accumulated as comprehensively as possible. In relation to vaccine issues, both 23vPPV and 7vPCV policy are important. There was strong support from the meeting for the recent recommendation from the Australian Technical Advisory Group on Immunisation that both 23vPPV (for those over 65 years) and 7vPCV (for those less than 2 years) be publicly funded as universal programs. With respect to the current programs, there were important issues for Aboriginal and Torres Strait Islander people for both 23vPPV and 7vPCV. For 23vPPV, research is required into both the utility and frequency of boosters in adults as well as any potential role for 7vPCV in adults. Improving the identification of Aboriginal and Torres Strait Islander children is important, especially in urban areas.

Australia↗
PubMed2003

Surveillance of adverse events following immunisation: Australia, 2000-2002.

The Adverse Drug Reactions Advisory Committee (ADRAC) database collates notifications of adverse events following immunisation (AEFI) from across Australia. The data were analysed for vaccines received between 1 January 2000 and 30 September 2002. Dose-based AEFI reporting rates were calculated using denominator data from the Australian Childhood Immunisation Register and annual national influenza vaccination coverage surveys. The majority of the 2,409 AEFI records analysed described non-serious events, principally injection site reactions; 10.5 per cent (n = 253) described AEFIs with outcomes defined as 'serious'. Ten deaths were recorded but only one, following yellow fever vaccine, was causally related to immunisation. The average annual population-based reporting rate was 4.5 per 100,000 population. Vaccine dose-based AEFI reporting rates were 2.2 per 100,000 doses of influenza vaccine for adults aged 40 years and over and 14.6 per 100,000 doses of all scheduled vaccines for children aged less than 7 years. The most frequently reported type of adverse event was injection site reaction following receipt of an acellular pertussis-containing vaccine, particularly among children in the age groups scheduled to receive their fourth or fifth doses of the vaccine (overall reporting rate 67 per 100,000 doses). The data highlight the safety of vaccines in Australia, and illustrate both the utility of available immunisation coverage data to estimate dose-based AEFI reporting rates and the value of the ADRAC database as a surveillance tool for monitoring AEFIs nationally.

Adolescent↗
PubMed2003

Progress towards eliminating Hib in Australia: an evaluation of Haemophilus influenzae type b prevention in Australia, 1 July 1993 to 30 June 2000.

The status of Haemophilus influenzae (Hib) disease and its prevention by vaccination was reviewed for the period 1997 to 2000. This forms the background to a change in national vaccine policy, from the use of two Hib vaccines to the use of PRP-OMP only throughout Australia from May 2000. Notifications of Hib in the 7-year period between 1993 and 2000 declined by 87 per cent among children 0-4 years of age; adjustment for likely under-reporting increase this to a 95 per cent reduction. Among age groups not included in the immunisation program, there was also a substantial decline in notified cases. Overall, a minimum 430 cases and 13 deaths were prevented by Hib immunisation annually in Australia. Enhanced Hib surveillance recorded 532 cases over seven years, with 353 in unvaccinated persons, 74 fulfilling criteria for true vaccine failure and 75 partially immunised. Of unvaccinated cases, 60 and 182 were eligible for routine and catch-up immunisation respectively. Although the overall incidence for 0-4 years of age declined from 15 to 1.2 cases per 100,000 population, the proportion of cases under six months of age increased from 11 per cent to 23 per cent. Overall vaccine effectiveness, estimated using data from the last five years of the program, was 83 per cent (95% CI 71-91%), increasing to 90 per cent (95% CI 83-94%) when adjusted for under-reporting to the Australian Childhood Immunisation Register. Among Aboriginal and Torres Strait Islander people, the incidence of invasive Hib disease fell from 4.6 cases per 100,000 population to 0.7 cases per 100,000 population but the proportion of cases now occurring among Aboriginal or Torres Strait Islander people increased significantly, from 7 to 15 per cent. The Hib immunisation program in Australia has been highly successful. Nevertheless, experience in Australia and elsewhere indicates that continued careful monitoring of Hib disease, with high quality laboratory surveillance, remains important.

Age Distribution↗
PubMed2002

Reactogenicity and immunogenicity of a live attenuated tetravalent measles-mumps-rubella-varicella (MMRV) vaccine.

In countries where routine varicella vaccination is implemented, it is usually given at the same age as that recommended for measles-mumps-rubella (MMR) vaccination. A combined multivalent measles-mumps-rubella-varicella (MMRV) vaccine would offer the convenience of a single injection and facilitate implementation of varicella vaccination into routine childhood immunisation schedules. We evaluated the immunogenicity and reactogenicity of a tetravalent MMRV candidate vaccine compared to an extemporaneous mix of a measles-mumps-rubella vaccine and varicella vaccine (MMR/V), and to a measles-mumps-rubella (MMR) vaccine alone. A multicentre study was conducted in which a total of 240 healthy children aged 12 months (80 per group) were randomised to receive MMRV, MMR/V, or MMR alone. Active surveillance for adverse events was undertaken for 43 days post-vaccination. Blood samples were taken prior to vaccination and at 60 days post-vaccination. There were no significant differences between groups in rates of pain, redness, or swelling at the site of vaccination. There was no significant difference in the rate of any fever (axillary temperature >or=37.5 degrees C) and grade 3 fever (axillary temperature >39.0 degrees C) between the groups receiving MMRV and MMR during the 43-day follow-up period. Although, a significant increase was found for fever of any cause with onset between days 0 and 14 for MMRV compared to the MMR group, there was no significant difference in grade 3 fever rates during the same period. With respect to immunogenicity, MMRV and MMR/V demonstrated similar seroconversion rates to each component compared to MMR alone, with at least 91.9% of subjects in all groups seroconverting to each vaccine component 60 days after vaccination. Decreased GMTs for varicella antibody at day 60 indicated that there may have been inhibition of this response compared to MMR/V. This tetravalent MMRV candidate vaccine showed promising results, although further examination of the possible increase in minor fever and decreased varicella immunogenicity should be assessed in future studies.

Antibodies, Viral↗
PubMed2002

Detecting and quantifying sunflower oil adulteration in extra virgin olive oils from the eastern mediterranean by visible and near-infrared spectroscopy.

One hundred and thirty-eight oil samples have been analyzed by visible and near-infrared transflectance spectroscopy. These comprised 46 pure extra virgin olive oils and the same oils adulterated with 1% (w/w) and 5% (w/w) sunflower oil. A number of multivariate mathematical approaches were investigated to detect and quantify the sunflower oil adulterant. These included hierarchical cluster analysis, soft independent modeling of class analogy (SIMCA method), and partial least squares regression (PLS). A number of wavelength ranges and data pretreatments were explored. The accuracy of these mathematical models was compared, and the most successful models were identified. Complete classification accuracy was achieved using 1st derivative spectral data in the 400-2498 nm range. Prediction of adulterant content was possible with a standard error equal to 0.8% using 1st derivative data between 1100 and 2498 nm. Spectral features and chemical literature were studied to isolate the structural basis for these models.

Food Contamination↗
PubMed2002

Nonpeptide bradykinin B2 receptor antagonists: conversion of rodent-selective bradyzide analogues into potent, orally-active human bradykinin B2 receptor antagonists.

The 1-(2-nitrophenyl)thiosemicarbazide (TSC) derivative, (S)-1-[4-(4-benzhydrylthiosemicarbazido)-3-nitrobenzenesulfonyl]pyrrolidine-2-carboxylic acid [2-[(2-dimethylaminoethyl)methylamino]ethyl]amide (bradyzide; (S)-4), was recently disclosed as a novel, potent, orally active nonpeptide bradykinin (BK) B2 receptor antagonist. The compound inhibited the specific binding of [3H]BK to NG108-15 cell membrane preparations (rodent neuroblastoma-glioma) expressing B2 receptors with a K(i) of 0.5 +/- 0.2 nM. Compound (S)-4 also demonstrated oral efficacy against Freund's complete adjuvant (FCA)-induced mechanical hyperalgesia in rats with an ED50 value of 0.84 micromol/kg. After we optimized the terminal binding determinants projecting from the TSC framework, we found that it was possible to replace the potentially toxicophoric nitro and divalent sulfur moieties with only a 15-fold loss in binding affinity ((S)-14a). However, bradyzide and its congeners were found to have much lower affinities for cloned human B2 receptors, expressed in Cos-7 cells. The hitherto synthesized TSC series was screened against the human B2 receptor, and the dibenzosuberane (DBS) pharmacophore emerged as the key structural requirement for potency. Incorporation of this group resulted in a series of derivatives ((S)-14d,e and 19b-d) with K(i) ranges of 10.7-176 nM in NG108-15 cells (expressing the rodent B2 receptor) and 0.79-253 nM in Cos-7 cells (expressing the human B2 receptor). There was no evidence of agonist activity with any of the nonpeptides in any of the cell lines tested. In vivo, oral administration of compound 19c reversed FCA-induced and turpentine-induced mechanical hyperalgesia in rodents with ED50 values of 0.027 and 0.32 micromol/kg, respectively. The selectivity profiles of compounds (S)-14f and (S)-14g were also assessed to determine the conformational and/or steric preferences of the double-ring arrangement. The affinity of (S)-14 g for the human B2 receptor suggested that it may be a hydrophobic interaction with the ethane bridge of the DBS moiety that accounts for the increased potency of compounds (S)-14d,e and 19b,c at this receptor, by favoring a binding mode inaccessible to the unsubstituted diphenylmethyl derivative, (S)-4.

Administration, Oral↗
PubMed2002

A heat-sensitive TRP channel expressed in keratinocytes.

Mechanical and thermal cues stimulate a specialized group of sensory neurons that terminate in the skin. Three members of the transient receptor potential (TRP) family of channels are expressed in subsets of these neurons and are activated at distinct physiological temperatures. Here, we describe the cloning and characterization of a novel thermosensitive TRP channel. TRPV3 has a unique threshold: It is activated at innocuous (warm) temperatures and shows an increased response at noxious temperatures. TRPV3 is specifically expressed in keratinocytes; hence, skin cells are capable of detecting heat via molecules similar to those in heat-sensing neurons.

Amino Acid Sequence↗
PubMed2002

A TRP channel that senses cold stimuli and menthol.

A distinct subset of sensory neurons are thought to directly sense changes in thermal energy through their termini in the skin. Very little is known about the molecules that mediate thermoreception by these neurons. Vanilloid Receptor 1 (VR1), a member of the TRP family of channels, is activated by noxious heat. Here we describe the cloning and characterization of TRPM8, a distant relative of VR1. TRPM8 is specifically expressed in a subset of pain- and temperature-sensing neurons. Cells overexpressing the TRPM8 channel can be activated by cold temperatures and by a cooling agent, menthol. Our identification of a cold-sensing TRP channel in a distinct subpopulation of sensory neurons implicates an expanded role for this family of ion channels in somatic sensory detection.

Amino Acid Sequence↗