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Biomedical subjects

P McIntyre

Publications and source records attributed to P McIntyre.

At least 55 records · Page 3Linked to original sources
PubMed1999

Australia's notifiable diseases status, 1997. Annual report of the National Notifiable Diseases Surveillance System.

In 1997 there were 89,579 notifications to the National Notifiable Diseases Surveillance System. A notable feature of 1997 was the pertussis outbreak which peaked towards the end of the year and resulted in 10,668 cases being notified. The highest number of notifications received was for hepatitis C (unspecified) with 19,692 notifications; this is the first year for which data have been reported for New South Wales and South Australia for this disease category. The number of measles cases rose after the low number reported in 1996 but is still well below the number reported in the outbreak years of 1993 and 1994. Rubella notifications continued to decline in 1997. Notifications of Haemophilus influenzae type b appeared to have stabilised at a low rate, having declined markedly after introduction of the conjugated vaccine in 1992. The number of cases of campylobacteriosis remained steady after having risen for several years. Notifications of hepatitis A cases rose considerably, much of this being due to one outbreak in New South Wales. The number of cases of salmonellosis rose while shigellosis numbers dropped slightly. Notifications for chlamydial infection and gonococcal infection continued to rise, whilst those for syphilis continued to fall.

Australia↗
PubMed1999

Sustained elevated levels of VCAM-1 in cultured fibroblast-like synoviocytes can be achieved by TNF-alpha in combination with either IL-4 or IL-13 through increased mRNA stability.

Rheumatoid arthritis is characterized by hyperplasia of the synovial lining and invasion of cartilage and bone by a subset of resident synovial cells named fibroblast-like synoviocytes. They are characterized by elevated expression of the vascular cell adhesion molecule-1 (VCAM-1). The intensity of VCAM-1 expression correlates with the degree of inflammation of the synovial joint. Differential VCAM-1 expression may determine inflammatory cell accumulation through its interaction with leukocytes that express the counterreceptor integrins alpha4beta1 and alpha4beta7. Elevated levels of VCAM-1 expression are thought to be a consequence of the presence of inflammatory mediators, in particular IL-1beta and TNF-alpha. Fibroblast-like synoviocytes rapidly up-regulate VCAM-1 expression in response to IL-1beta and TNF-alpha, but also to IL-4. However, we now show that the response to IL-1beta or TNF-alpha is of a brief transient nature, even when applied continuously over a period of 12 days, whereas the response to IL-4 or IL-13 is sustained. Great synergy is obtained by combining either IL-4 or IL-13 with TNF-alpha, which results in a highly elevated but also sustained expression of VCAM-1. The mechanism by which IL-4 or IL-13 prolongs VCAM-1 expression can be explained by a dramatic increase in the half-life of VCAM-1 mRNA.

Arthritis, Rheumatoid↗
PubMed1999

The pre-operative ECG in day surgery: a habit?

As the population presenting for day-case surgery and anaesthesia increases, so does the challenge of adequate pre-operative assessment. Although an electrocardiogram is frequently performed, its value in day-case surgery remains unproven. One thousand, one hundred and eighty-five patients presenting for day-case surgery were assessed. One hundred and fifty-four (13%) were referred for electrocardiogram according to well-recognised criteria for the prediction of coronary artery disease. They were read independently by the anaesthetist responsible for the case and by an experienced cardiologist. A significant abnormality was noted in 26% of electrocardiograms, most frequently in patients referred with hypertension. There was a good correlation between the reports of the anaesthetist and cardiologist. Only 20% of those patients with an abnormal electrocardiogram had their surgery postponed. No adverse events occurred in patients proceeding to surgery despite the abnormalities. We conclude that a resting electrocardiogram is of limited value in risk stratification of patients undergoing day-case surgery.

Adult↗
PubMed1999

Health care incentives in immunisation.

BACKGROUND: Australia has introduced a nationwide immunisation incentive scheme. This yet to be evaluated two-year program offers financial rewards to providers and parents to encourage childhood immunisations. OBJECTIVES: To review the use of incentives in immunisation uptake, identify issues in developing an incentive program for childhood immunisation and examine the findings within the context of the Australian scheme. METHOD: Medline was searched under 'immunization and financial incentive' and 'immunization and incentive' in English 1966 to 1998. RESULTS: The search identified six and 93 articles respectively, of which six examined the role of material incentives influencing coverage of immunisation. References and reviews identified a further three studies. Among these nine studies (two British, six American, one Nicaraguan), two reported the same intervention. Of the eight incentives examined, four referred to non-financial incentives such as food vouchers and four to monetary incentives for parents (1) or providers (3). Groups receiving the incentives were up to three times more likely to be immunised and had overall immunisation rates up to 17% higher than comparison groups. CONCLUSIONS: Effective incentives require collaboration of key players, using a program appropriate to the characteristics of the population. Although varying in cost-effectiveness, both monetary and non-monetary incentives can improve childhood immunisation uptake. Evaluation of current programs including the Australian ones will assist future allocation of resources.

Child↗
PubMed1998

A simple modelling approach for water quality: the example of an estuarine impoundment.

With the increasing development of water quality standards for all forms of water bodies and all forms of their uses, there is a greater need for models that can predict water quality in relation to these standards. This paper proposes an empirical method based on logistic regression techniques that deliver probabilities that given quality standards are met (i.e. water above or below the given standard). This technique is applied to data from a saline intrusion barrage (River Wansbeck, Northumberland, England) to predict low water quality events on the basis of UK water standards. The approach accurately classifies the overwhelming majority of pollution events that are caused by processes internal to the system. Misclassification can be ascribed to external processes, such as combined sewer outfalls. The general applicability of this method is compared to physically-based models.

Ammonia↗
PubMed1998

Capsaicin sensitivity is associated with the expression of the vanilloid (capsaicin) receptor (VR1) mRNA in adult rat sensory ganglia.

A vanilloid receptor (VR1) has recently been cloned and shown to be a target for capsaicin, the excitotoxic component of capsicum peppers (Caterina, M.J., Schumacher, M.A., Tominaga, M., Rosen, T.A., Levine, J.D. and Julius, D., Nature, 389 (1997) 816-824). The effects of capsaicin appear to be selective for a subset of sensory neurones which includes polymodal nociceptors. The present study describes the distribution of VR1 mRNA, together with measurements of capsaicin sensitivity, in sensory nerve ganglia of different embryological origins and a single sympathetic ganglion, the superior cervical ganglion (SCG). In situ hybridisation revealed the expression of VR1 mRNA in small-to-medium-sized neurones of the dorsal root, trigeminal and vagal ganglia. No hybridisation signal was observed in the SCG neurones. This pattern of expression correlated with capsaicin sensitivity measured by whole-cell voltage clamp where, in similar sized cells, over 80% of neurones from dorsal root and vagal ganglia were capsaicin sensitive, but all SCG neurones were insensitive to capsaicin.

Animals↗
PubMed1998

Pertussis vaccines: past, present and future in Australia.

In August 1997, a workshop was convened by the National Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases to consider current issues in the use of pertussis vaccines and implications for the Australian immunisation schedule. Topics covered included the history, efficacy and reactogenicity of whole-cell and acellular vaccines and vaccine schedules. Acellular pertussis vaccine is preferred by the National Health and Medical Research Council for the primary course as well as the 18 month and 4-5 year old childhood doses. At the time of the workshop, a 3-component acellular vaccine (DTPa) had been approved (licensed) in Australia for all doses in the childhood schedule. It was the first vaccine subject to a cost-effectiveness evaluation under the new vaccine funding arrangements. Issues considered in the evaluation of the cost-effectiveness of the vaccine were discussed. These included comparative efficacy, adverse events and compliance, and the question of community as well as individual benefit from the use of the vaccine.

Australia↗
PubMed1998

Comparative, general pharmacology of SDZ NKT 343, a novel, selective NK1 receptor antagonist.

1. The in vitro and in vivo pharmacology of SDZ NKT 343 (2-nitrophenyl-carbamoyl-(S)-prolyl-(S)-3-(2-naphthyl)alanyl-N-benzyl-N- methylamide), a novel tachykinin NK1 receptor antagonist was investigated. 2. SDZ NKT 343 inhibited [3H]-substance P binding to the human NK1 receptor in transfected Cos-7 cell membranes (IC50 = 0.62+/-0.11 nM). In comparison, in the same assay Ki values for FK888, CP 99,994, SR 140,333 and RPR 100,893 were 2.13+/-0.04 nM, 0.96+/-0.20 nM, 0.15+/-0.06 nM and 1.77+/-0.41 nM, respectively. SDZ NKT 343 showed a markedly lower affinity at rat NK1 receptors in whole forebrain membranes (IC50 = 451+/-139 nM). 3. SDZ NKT 343 caused an increase in EC50 as well as reduction in the number of binding sites (Bmax) determined for [3H]-substance P, suggesting a non-competitive interaction at the human NK1 receptor. SDZ NKT 343 also caused a reduction in the maximum elevation of [Ca2+]i evoked by substance P (SP) in human U373MG cells and depressed the maximum [Sar9]SP sulphone-induced contraction of the guinea-pig isolated ileum. The antagonism of SP effects on U373MG cells by SDZ NKT 343 was reversible. 4. SDZ NKT 343 showed weak affinity to human NK2 and NK3 receptors in transfected Cos-7 cells (Ki of 0.52+/-0.04 microM and 3.4+/-1.2 microM, respectively). SDZ NKT 343 was inactive in a broad array of binding assays including the bradykinin B2 receptor the histamine H1 receptor, opiate receptors and adrenoceptors. SDZ NKT 343 only weakly inhibited the voltage-activated Ca2+ and Na+ currents in guinea-pig dorsal root ganglion neurones. The enantiomer of SDZ NKT 343, (R,R)-SDZ NKT 343 was about 1000 times less active at human NK1 receptors expressed in Cos-7 cell membranes. 5. Contractions of the guinea-pig ileum by [Sar9]SP sulphone were inhibited by SDZ NKT 343 in a concentration-dependent manner, with an IC50 = 1.60+/-0.94 nM, while the enantiomer (R,R)-SDZ NKT 343 was 100 times less active (IC50 = 162+/-26 nM). In comparison, in the same assay IC50 values for other NK1 receptor antagonists CP 99,994, SR 140,333, RPR 100,893 and FK 888 were 2.90+/-07 nM, 0.14+/-0.02 nM, 11.4+/-2.9 nM and 2.4+/-0.83 nM, respectively. 6. In anaesthetized guinea-pigs i.v. administered SDZ NKT 343 antagonized [Sar9]SP sulphone-evoked bronchoconstriction (70% reduction at 0.4 mg kg(-1), i.v.). Basal airway resistance, mean arterial blood pressure and heart rate were not affected. 7. In conclusion, SDZ NKT 343 is a highly selective NK1 receptor antagonist with high potency at the human and guinea-pig receptors. SDZ NKT 343 may be used as a potential novel therapeutic agent in human diseases where NK1 receptor hyperfunction is involved.

Animals↗
PubMed1998

Geographic differences in bacterial meningitis: less may be as interesting as more.

Many reports in the last decade have described populations with a high incidence of bacterial meningitis, especially amongst indigenous groups in industrialised countries, such as North American Eskimos and Apache Indians and Australian Aborigines, particularly with meningitis due to Haemophilus influenzae type b (Hib). Lack of evidence that invasive Hib disease, including meningitis, is a significant health problem has been attributed to lack of appropriate data, either due to lack of laboratory and clinical facilities, such as in most less industrialised countries, or lack of study. Host differences in immune response, though known to be important for individual susceptibility to Hib disease and bacterial meningitis, have not been thought important on a population level. Good quality epidemiologic data now available from Hong Kong and Japan, based on sound laboratory methods, have shown bacterial meningitis, particularly due to Hib and Neisseria meningitidis, to be significantly less common than in predominantly Caucasian populations in various industrialised countries. Differences in host immune response to these capsular polysaccharides seems the most likely explanation for this observation. It is interesting that other immunologically mediated disorders such as Kawasaki disease and systemic lupus erythematosis have a relatively high incidence in Sino Japanese populations, lending plausibility to inherited differences in immune response as a mechanism for these observations.

Global Health↗
PubMed1998

Prevention of serious bacterial infection in children with nephrotic syndrome.

Although nephrotic syndrome is well known as a predisposing factor to bacterial infection in children, especially peritonitis due to Streptococcus pneumoniae, data on the incidence of infection and the effectiveness of preventative measures are limited. With particular reference to pneumococcal disease, this review summarises the available data on the pattern and incidence of invasive bacterial infection in children with nephrotic syndrome, and the level of evidence for the use of penicillin chemoprophylaxis and pneumococcal immunisation. Although data on the effectiveness of pneumococcal immunization in children with nephrotic syndrome are limited, the safety profile of this vaccine makes the risk-benefit ratio favourable to use of the current polysaccharide vaccine in those over 2 years of age. Conjugate pneumococcal vaccines are likely to be more effective, particularly in children under 2 years of age and should be available by the year 2000. Although penicillin prophylaxis against pneumococcal infection is not of proven benefit for nephrotic syndrome, it is beneficial in sickle cell disease without appreciable risk. Subgroups of patients with nephrotic syndrome most likely to benefit from twice daily phenoxymethyl penicillin prophylaxis include children under 2 years of age, with unresponsive or frequently relapsing disease, or who have had a previous episode of pneumococcal infection.

Antibiotic Prophylaxis↗
PubMed1998

Pneumocystis carinii pneumonia: pitfalls of prophylaxis.

Pneumocystis carinii pneumonia (PCP) occurs commonly in immunocompromised patients. Sulfamethoxazole-trimethoprim (SMX-TMP) is effective prophylaxis, although PCP may still occur despite apparently adequate use. We report three cases of PCP which highlight some of the pitfalls of prophylaxis.

Anti-Infective Agents↗
PubMed1998

Uptake, yield of neoplasia, and adverse effects of flexible sigmoidoscopy screening.

BACKGROUND: A multicentre randomised controlled trial to evaluate screening by "once only" flexible sigmoidoscopy (FS) for prevention of bowel cancer is in progress. AIMS: To pilot the trial protocol examining rates of attendance, yield of neoplasia, and adverse effects. SUBJECTS: A total of 3540 subjects aged 55-64 years in Welwyn Garden City (WGC) and 19,706 in Leicester (LE). METHODS: Subjects responding positively to an "interest in screening" questionnaire were randomised to invitation for screening or control arms. Small polyps were removed during screening. Colonoscopy was undertaken for high risk polyps (more than two adenomas, size at least 1 cm, villous histology, severe dysplasia, or malignancy). The remainder were discharged. RESULTS: In WGC and LE respectively, 59% and 61% indicated an interest in screening, of which 74% and 75% attended. Adenomas were detected in 10% and 9%, respectively, and cancers in 7 per 1000 (in both centres), 55% at Dukes's stage A. The colonoscopy referral rate was 6% in both centres. Mild, short lived bleeding occurred in 3%. One person died following surgery. CONCLUSIONS: Compliance rates, yield of adenomas, and referral rate for colonoscopy were as expected, but cancer detection rates were higher. Adverse effects following sigmoidoscopy or colonoscopy were mild and transient, but there was one postoperative death. A randomised trial is necessary to evaluate fully the risks and benefits of this intervention.

Adenoma↗
PubMed1997

Epidemiology and prevention of pneumococcal disease.

There are comparatively little data on the incidence and morbidity from pneumococcal disease in Australia and elsewhere. Available data suggest that the overall incidence of invasive pneumococcal disease in Australia is comparable with similar populations. Very high rates are reported in Central Australian Aborigines, similar to invasive Haemophilus influenzae type b (Hib) disease. Disease incidence is probably greatly underestimated by case ascertainment from sterile site isolates alone. New diagnostic methods, such as serology to detect components of the pneumococcal cell wall, promise to significantly enhance detection of pneumococci as a cause of pneumonia, especially in childhood, but are epidemiologic rather than clinical tools. Resistance to penicillin and other antibiotics is an increasing problem worldwide, promoted by excessive antibiotic use, especially in children. This has focused attention on vaccine prevention. Fortunately, antibiotic-resistant pneumococci appear to belong to a limited range of serotypes, those commonly colonising children, in all areas so far studied. If conjugate pneumococcal vaccines prove to eradicate carriage, in a similar fashion to conjugate Hib vaccines, vaccination may be the major weapon against the spread of antibiotic-resistant pneumococcal infection. Conjugate pneumococcal vaccines are now in large scale efficacy trials, with outcomes of bacteraemia (California) and otitis media (Finland). Results of these trials are eagerly awaited.

Australia↗
PubMed1997

Complex CD44 splicing combinations in synovial fibroblasts from arthritic joints.

CD44 is a broadly expressed cell surface glycoprotein which is the major cell surface receptor for the glycosaminoglycan, hyaluronan. In humans, alternative splicing of up to 9 variant exons (v2-v10) into CD44 mRNA, together with post-translational modification via glycosylation and chondroitin sulfate attachment has the potential of generating a large number of CD44 isoforms. Insertion of these various exons has the potential to change the functional capacities of the molecule and has implications in disease. We have analyzed CD44 splice variant expression in cultured VCAM-1-positive synovial fibroblasts isolated from patients with osteo- or rheumatoid arthritis and from normal synovium. Rheumatoid and osteoarthritic tissue express CD44 splice variants at the cell surface level. At the mRNA level exons v3, v6, v7, v8, v9 and v10 were detected in different splicing combinations. Rheumatoid tissue showed high expression, osteoarthritic tissues showed great variation. In contrast, non-inflamed tissue showed no splicing events. Our results indicate that the nature of CD44 splice variant expression may be linked to the inflammatory state of the synovial joint.

Alternative Splicing↗