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Biomedical subjects

P McIntyre

Publications and source records attributed to P McIntyre.

At least 73 records · Page 4Linked to original sources

Epidemiology and prevention of pneumococcal infections.

There are comparatively few data on the incidence and morbidity from pneumococcal disease, which is greatly underestimated by case ascertainment from sterile site isolates alone. New diagnostic methods, such as serology and polymerase chain reaction, to detect components of the pneumococcal cell wall promise to significantly enhance detection of pneumococci causing childhood pneumonia. There is increasing evidence that excessive antibiotic use in children is a major factor promoting antibiotic resistance in pneumococci. Resistance is a problem worldwide and has focused attention on vaccine prevention. Fortunately, antibiotic-resistant pneumococci appear to belong to a limited range of serotypes, those commonly colonizing children, in all areas so far studied. If conjugate pneumococcal vaccines prove to eradicate carriage, immunization may be the major weapon against the spread of antibiotic-resistant pneumococcal infection. Conjugate pneumococcal vaccines are now being studied in large-scale efficacy trials with outcomes of bacteremia and otitis media, the results of which are eagerly awaited.

Bacterial Vaccines↗

Evaluation of a protocol for selective empiric treatment of fever without localising signs.

A protocol for management of young febrile children at risk for bacteraemia has been used at Westmead Hospital, a university based hospital in the western Sydney region, since early 1994. Implementation of the protocol was retrospectively evaluated for the 12 month period 1 June 1994 to 31 May 1995, using the emergency department log book as the primary data source. Altogether 498 children, aged from 3 months to 3 years, with a fever > or = 39.5 degrees C were identified over this period, of whom 291 were admitted to hospital because of evidence of sepsis or identified focal infection and 207 children without focal infection were observed in the short stay annexe of the emergency department. Fifty children, considered at high risk of bacteraemia because of a total white cell count > or = 20 x 10(9)/1 received empiric antibiotic treatment with ceftriaxone, of whom 19 subsequently had proved bacteraemia and another 10 had focal infection identified during observation in the short stay annexe. Bacteraemia was due to Streptococcus pneumoniae in 16 cases and Haemophilus influenzae type b in three. No adverse events occurred at follow up. Use of a management protocol and selection on higher white cell count criterion than previously recommended by US centres resulted in restriction of empiric antibiotic treatment to a small proportion of young febrile children presenting to a busy emergency department of whom 38% were bacteraemic.

Bacteremia↗

Acyclovir for the prevention and treatment of varicella zoster in children, adolescents and pregnancy.

Varicella causes a mild, self-limiting childhood disease that may reactivate years later as shingles. In immunocompromised patients with altered cell mediated immunity, and rarely in healthy individuals, varicella results in a life-threatening infection. The antiviral drug, acyclovir, substantially reduces the mortality and risk of severe disease in these groups of patients. Early commencement of acyclovir is recommended for children with both varicella and altered cell mediated immunity, newborns during the first 2 weeks of life, preterm infants in the neonatal nursery, and severe varicella or shingles (including ocular zoster) in any patient, as well as during pregnancy. Acyclovir may be considered in children with serious cardiopulmonary disease or chronic skin disorders where varicella may exacerbate the underlying disease or increase the risk of secondary bacterial sepsis. Acyclovir, however, is not recommended for healthy individuals without severe disease, as a prophylactic agent against varicella, for asthmatics receiving aerosolized or low-dose oral steroids and/or as treatment of the post-varicella syndromes. When acyclovir is prescribed it should be given intravenously to those with severe disease, those at risk of dissemination and in children younger than 2 years of age.

Acyclovir↗

Automated sample preparation for cholesterol determination in foods.

An automated sample preparation system has been developed for the determination of cholesterol in a wide range of matrices. Isolation of cholesterol is performed with a robotic arm coupled with a series of modular stations. Samples are introduced into the system which adds the appropriate reagents, carries out the saponification, pH adjustment, solid-phase extraction and drying steps. This system was evaluated using 15 different food matrices. The average recovery for NIST standards exceeded 97%. A solution of n-hexane-2-propanol was substituted for the traditional methanol-chloroform extraction. Manual pH adjustment was replaced with a buffer. Manual and automated methods were compared and no difference was observed at the 95% confidence level.

Automation↗

Lumbar puncture in suspected neonatal sepsis.

OBJECTIVE: The importance of lumbar puncture (LP) as part of the evaluation of suspected neonatal sepsis is assessed, as it may be the only positive diagnostic test in about 10% of septic babies with meningitis but negative blood cultures. However, LP may compromise respiratory function, and the interpretation of cerebrospinal fluid (CSF) may not be straightforward. CONCLUSION: The clinical setting and the probability of meningitis are important determinants of the likely value of LP. For asymptomatic neonates with obstetric risk factors for sepsis, and for babies with early-onset respiratory distress alone, LP may be delayed and only performed later if blood cultures are positive. This is because hundreds of LP will be needed to diagnose a single case. However, infants with suspected late-onset sepsis should have an immediate LP because finding Gram-negative bacilli or fungi in the CSF will affect treatment choices.

Humans↗

Prevention of neonatal group B streptococcal sepsis: is routine antenatal screening appropriate.

Four strategies for prevention of early onset neonatal group B streptococcal (GBS) sepsis were considered: A: routine antenatal screening for GBS vaginal carriage at 26-28 weeks' gestation and intrapartum antibiotic prophylaxis for all carriers; B: screening as above and prophylaxis only for carriers with risk factors for sepsis; C: prophylaxis for all women with risk factors; D: as for C plus screening at 37 weeks' gestation and prophylaxis for carriers. The outcomes considered for each option were: the proportion of women given prophylaxis; the risk of anaphylaxis; cases of neonatal GBS sepsis and deaths prevented; costs of screening, prophylaxis and of acute care of remaining cases. Published local and overseas studies of neonatal GBS sepsis, effectiveness of antenatal screening and prophylaxis and estimated costs were evaluated. Any of the proposed strategies can prevent a significant proportion of cases of neonatal GBS sepsis and a strategy for prevention of neonatal group B streptococcal sepsis should be part of routine obstetric practice. Strategy C is simple, effective, inexpensive and avoids unnecessary antibiotic use; it is recommended particularly when antenatal care is provided mainly in community or private practice. Strategy A (using vaginal and rectal swabs for screening) could prevent more cases, but at greater cost which could be justified only if protocols can be properly implemented and monitored.

Australia↗

Internal quality assurance in a clinical virology laboratory. I. Internal quality assessment.

AIMS: In April 1991 an internal quality assessment scheme (IQAS) was introduced into the virology section of the Clinical Microbiology and Public Health Laboratory, Cambridge. The IQAS was established to identify recurring technical and procedural problems, to check the adequacy of current techniques, and to calculate the frequency of errors. METHODS: Between April 1991 and December 1993, 715 anonymous clinical serum samples were submitted to the laboratory to test 3245 individual procedures of diagnostic viral serology. RESULTS: A total of 485 (14.9%) procedural and 61 (1.9%) technical discrepancies were observed, the technical discrepancies mainly being recorded in complement fixation tests. Twenty two (0.7% of total procedures) of the technical discrepancies were diagnostically significant. CONCLUSIONS: Evaluation criteria developed with the introduction of IQAS to viral serology, and technical and procedural discrepancies are assessed. As yet, IQAS has not been introduced to other sections of the diagnostic virology laboratory (virus isolation, electron microscopy, immunofluorescence, and enzyme linked immunosorbent assays for viral and chlamydial antigens).

Humans↗

Internal quality assurance in a clinical virology laboratory. II. Internal quality control.

AIMS: In April 1991 additional quality control procedures were introduced into the virology section of the Clinical Microbiology and Public Health Laboratory, Cambridge. Internal quality control (IQC) samples were gradually included in the serological assays performed in the laboratory and supplemented kit controls and standard sera. METHODS: From April 1991 to December 1993, 2421 IQC procedures were carried out with reference sera. RESULTS: The IQC samples were evaluated according to the Westgard rules. Violations were recorded in 60 of 1808 (3.3%) controls and were highest in the IQC samples of complement fixation tests (25/312 (8%) of controls submitted for complement fixation tests). CONCLUSIONS: The inclusion of IQC samples in the serological assays performed in the laboratory has highlighted batch to batch variation in commercial assays. The setting of acceptable limits for the IQC samples has increased confidence in the validity of assay results.

Complement Fixation Tests↗

Molecular studies on kinin receptors.

We describe the results of functional studies on DNA clones encoding functional bradykinin receptors derived from human, rat, and mouse sources and including both genomic and complementary DNA clones. In both the Xenopus oocyte and the COS cell expression systems, the receptors from human and rat showed the pharmacological properties of B2 receptors, but receptors from mouse displayed both B1- and B2-like pharmacological properties. We further investigated the molecular relationship between the B1 and B2 receptor subtypes expressed by a human fibroblast cell line, and we demonstrate that these two receptor subtypes are encoded by distinct mRNA species.

Amino Acid Sequence↗

B1 and B2 bradykinin receptors encoded by distinct mRNAs.

Bradykinin receptors have been subdivided into at least two major pharmacological subtypes, B1 and B2. The cDNAs encoding functional B2 receptors have recently been cloned, but no molecular information exists at present on the B1 receptor. In this article, we describe experiments examining the possible relationship between the mRNAs encoding the B1 and B2 types of receptor. We showed previously that the human fibroblast cell line WI38 expresses both B1 and B2 receptors. In this report, we describe oocyte expression experiments showing that the B1 receptor in WI38 human fibroblast cells is encoded by a distinct mRNA approximately 2 kb shorter than that encoding the B2 receptor. We have used an antisense approach in conjunction with the oocyte expression system to demonstrate that the two messages differ in sequence at several locations throughout the length of the B2 sequence. Taken together with the mixed pharmacology exhibited in some expression systems by the cloned mouse receptor, the data indicate that B1-type pharmacology may arise from two independent molecular mechanisms.

Amino Acid Sequence↗

An economic analysis of alternatives for childhood immunisation against Haemophilus influenzae type b disease.

Cost-effectiveness and cost-utility analyses of immunisation strategies against invasive Haemophilus influenzae type b (Hib) disease in Australia were based on a hypothetical birth cohort of 250,000 non-Aboriginal Australian children. The model predicted that, without immunisation, 625 cases of invasive Hib disease would occur in under-five-year-olds, with direct costs of $10.2 million. Universal public sector vaccination beginning before six months of age (6MVAC) prevented 80 per cent of cases; vaccination at 12 months (12MVAC) 62 per cent and at 18 months (18MVAC) 46 per cent. At a vaccine cost of $15 per dose, 18MVAC gave the lowest cost per quality-adjusted life year (QALY) over a wide range of model assumptions, with 6MVAC the 'best' alternative. The best estimate ($ per QALY) for 6MVAC was $6930 (three doses), for 12MVAC $9136 (two doses) and for 18MVAC $1231 (one dose). The cost per QALY of single dose catch-up immunisation of older children was estimated at $8630 at two years, $27,000 at three years and $117,000 at four years if done at a scheduled visit; these values were increased if an additional medical visit was included. The threshold cost per vaccine dose at which an immunisation program became cost-saving was estimated for 6MVAC, 12MVAC and 18MVAC as $11, $10 and $14. Even under a worst-case scenario, an immunisation program at 6, 12 or 18 months became cost-saving if indirect costs of death were included. Comparison with previous analyses revealed the importance of the incidence and age distribution of disability and assumptions about vaccine administration costs in determining model outcomes.

Child↗