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Biomedical subjects

P Mackay

Publications and source records attributed to P Mackay.

At least 19 recordsLinked to original sources
PubMed2000

Mapping of obesity QTLs in a cross between mouse lines divergently selected on fat content.

A genome-wide quantitative trait locus (QTL) analysis was performed in a polygenic obesity mouse model resulting from a long-term selection experiment. The parental lines were outbred lines divergently selected for 53 generations for high-fat (fat, F line) or low-fat (lean, L line) percentage (fat%) that differed fivefold in fat% at 14 weeks of age. An F2 population of 436 mice was used for the QTL analysis with 71 markers distributed across the genome. The analysis revealed significant QTLs Fob1 (for F-line obesity QTL 1), Fob2, Fob3, and Fob4, on Chromosomes (Chrs) 2, 12, 15, and X, respectively. None of these QTLs map to regions of known single gene obesity mutations (Lepob, Leprdb, Cpefat, Ay, tub), though they map to regions of previously described obesity QTLs and candidate genes. The effects of Fob1, Fob3, Fob4 were additive, and that of Fob2 was dominant. Fob2 also showed a significant female-specific effect. Fob1, Fob2, Fob3, and Fob4 explained 4.9%, 19.5%, 14.4%, and 7.3% of the F2 phenotypic variance for fat%, respectively. This study identified four loci that contributed to the response to divergent selection and control a significant proportion of the difference in obesity between the F and L lines.

Animals↗
PubMed1998

Changes in auxin response from mutations in an AUX/IAA gene.

Transcription of the AUX/IAA family of genes is rapidly induced by the plant hormone auxin, but evidence that AUX/IAA genes mediate further responses to auxin has been elusive. Changes in diverse auxin responses result from mutations in the Arabidopsis AXR3 gene. AXR3 was shown to be a member of the AUX/IAA family, providing direct evidence that AUX/IAA genes are central in auxin signaling. Molecular characterization of axr3 gain-of-function and loss-of-function mutations established the functional importance of domains conserved among AUX/IAA proteins.

Amino Acid Sequence↗
PubMed1997

Randomised controlled double blind study of role of recombinant erythropoietin in the prevention of chronic lung disease.

AIM: To evaluate the role of recombinant human erythropoietin (R-HuEpo) in reducing iron infusion, which may exacerbate free radical damage, leading to chronic lung disease. METHODS: A multicentre, randomised, placebo controlled, double blind study was carried out in four neonatal intensive care units in Yorkshire. Infants were randomly allocated and received either R-HuEpo (480 U/kg/wk) or placebo by twice weekly subcutaneous injection. The primary outcome measure was the number of days on respiratory support and a secondary outcome the number of blood transfusions required. RESULTS: Forty two very low birthweight (VLBW) infants were randomly allocated. There was little difference in the need for respiratory support one month after randomisation, but subsequently there was a trend towards a reduction in the proportion requiring respiratory support in the R-HuEpo group (difference at three months -0.50, 95% confidence interval -1.00, 0.17). During stay in hospital, the median number of blood transfusions was lower for infants in the R-HuEpo group (difference in medians -2, 95% CI -4, 0). The study was stopped early because of failure to recruit babies at the expected rate. CONCLUSIONS: R-HuEpo seems to reduce the number of days in oxygen for ill VLBW infants. These data could be used to construct a larger multicentre study to evaluate this effect further.

Blood Transfusion↗
PubMed1997

Treatment with GAD65 or BSA does not protect against diabetes in BB rats.

The M(r) 65,000 isoform of glutamic acid decarboxylase (GAD65) has been implicated as the initiating islet cell antigen in the pathogenesis of diabetes, primarily based on studies in non-obese diabetic (NOD) mice. To test the role of this islet cell autoantigen in the pathogenesis of spontaneously occurring diabetes in another animal model, purified recombinant human islet GAD65 was injected i.v. at 200 micrograms/animal into 18-day-old diabetes-prone BB rats. For controls, bovine serum albumin (BSA), which has also been implicated in the pathogenesis of diabetes, or buffer alone was injected into age matched BB rats. At 210 days of age there were no differences in diabetes incidence in the 3 groups, i.e. 73% (11 of 15) in the GAD65-treated, 81% (13 of 16) in the BSA-treated and 65% (11 of 17) in the buffer-treated animals, or in the median age at onset of disease, i.e. 79 days (range 65-111), 87 days (range 60-107) and 86 days (range 74-109), respectively. The lack of protection against diabetes following GAD65 treatment could hypothetically be explained by no or by an aberrant expression of GAD in BB-rat islet cells. However, immunohistochemistry of pancreata and immunoblotting analysis of isolated islets showed that the expression of GAD65 and GAD67 was similar in BB and Lewis rats. In conclusion, these data indicate that neither GAD65 nor BSA autoimmunity is important for the development of diabetes in BB rats, in contrast to the situation in NOD mice, and further emphasizes that extrapolation from only one animal model to autoimmune diabetes in general may not be appropriate.

Animals↗
PubMed1993

The Australian Incident Monitoring Study: an analysis of 2000 incident reports.

The Australian Patient Safety Foundation was formed in 1987; it was decided to set up and co-ordinate the Australian Incident Monitoring Study as a function of this Foundation; 90 hospitals and practices joined the study. Participating anaesthetists were invited to report, on an anonymous and voluntary basis, any unintended incident which reduced, or could have reduced, the safety margin for a patient. Any incident could be reported, not only those which were deemed "preventable" or were thought to involve human error. The Mark I AIMS form was developed which incorporated features and concepts from several other studies. All the incidents in this symposium were reported using this form, which contains general instructions to the reporter, key words and space for a narrative of the incident, structured sections for what happened (with subsections for circuitry incidents, circuitry involved, equipment involved, pharmacological incidents and airway incidents), why it happened (with subsections for factors contributing to the incident, factors minimising the incident and suggested corrective strategies), the type of anaesthesia and procedure, monitors in use, when and where the incident happened, the experience of the personnel involved, patient age and a classification of patient outcome. Enrollment, reporting and data-handling procedures are described. Data on patient outcome are presented; this is correlated with the stages at which the incident occurred and with the ASA status of the patients. The locations at which the incidents occurred and the types of procedures, the sets of incidents analysed in detail and a breakdown of the incidents due to drugs are also presented.(ABSTRACT TRUNCATED AT 250 WORDS)

Accidents↗
PubMed1993

The Australian Incident Monitoring Study. The "wrong drug" problem in anaesthesia: an analysis of 2000 incident reports.

Amongst the first 2000 incidents reported to the Australian Incident Monitoring Study, there were 144 incidents in which the "wrong drug" was nearly or actually administered to a patient. Thirty-three percent of the incidents involved ampoules and just over 40% syringes; in over half of the latter the syringes were of the same size, and also, in over half, they were correctly labelled. In 81% of the 144 incidents the "wrong drug" was actually given. This was more common with syringes (93%) than ampoules (58%). Thus the most common error was actually giving the wrong drug from a correctly labelled syringe. The most common drug involved was a muscle relaxant in both ampoule and syringe incidents. In 74% of all reports, there was the potential for serious harm to the patient; however no deaths were reported. Factors which contributed significantly to the incidents were similar appearance, inattention and haste. "Failure of communication" was a significant factor in syringe incidents when two or more staff were involved. The only significant factor which minimised the outcome was rechecking of the syringe or drug ampoule before giving the drug. Strategies suggested to address the "wrong drug" problem include education of staff about the nature of the problem and the mechanisms involved; colour coding of selected drug classes for both ampoules and syringes; the use of standardised drug storage, layout and selection protocols; having a drawing up and labelling convention; and the use of checking protocols.

Anesthesia↗
PubMed1993

The Australian Incident Monitoring Study. Clinical anaphylaxis: an analysis of 2000 incident reports.

There were 57 reports of possible allergic reactions in the perioperative period in the first 2000 incidents reported to the Australian Incident Monitoring Study. These were examined and classified with respect to presentation, clinical course, agents implicated and management strategies employed. Reactions were graded as to probability of allergic aetiology and severity of systemic disturbance. Two deaths were reported. A method of determining an "allergy score" was devised as an indication of which reactions may be most deserving of further investigation.

Anaphylaxis↗
PubMed1993

The Australian Incident Monitoring Study. Recovery room incidents in the first 2000 incident reports.

Of the first 2000 incidents reported to the Australian Incident Monitoring Study 120 (6%) occurred in the recovery room after general, regional or local anaesthesia. Over two thirds (69%) of these involved the respiratory system, 19% were cardiovascular, 3% involved the central nervous system and 9% were miscellaneous in nature. These recovery room incidents were associated with significantly more adverse outcomes (56%) than incidents in the operating theatre (24%). The types and relative frequencies of these recovery room incidents were similar to those of serious recovery complications in a recent analysis of closed malpractice claims; this suggests that incident monitoring may be useful in the study and prevention of recovery room complications. Over three quarters (77%) of all recovery incidents (and 88% of respiratory incidents) were detected clinically; the remainder were first detected by a monitor. A theoretical analysis showed that over 95% of respiratory events, had they been allowed to evolve, would have been detected by pulse oximetry before organ damage occurred, emphasising the potential importance of pulse oximetry in reducing adverse outcome from any complication in the recovery ward which might be "missed" by clinical observation. The findings of this study underline the importance of having an adequate number of trained recovery nursing staff supported by the availability of a pulse oximeter for each patient at least until the return of protective reflexes and the ability to maintain adequate arterial saturation has been established.

Accidents↗
PubMed1986

Islet cell and other organ-specific autoantibodies in healthy first-degree relatives to insulin-dependent.

The presence of organ-specific autoantibodies including islet cell surface, cytoplasmic and cytotoxic as well as thyroid-gastric antibodies were determined in healthy, non-diabetic, first-degree relatives to 30 insulin-dependent diabetic (IDDM) children. Thirty healthy families without family-history of diabetes mellitus served as controls. The prevalence of organ-specific autoantibodies among the healthy members in the diabetic families was increased compared to the control families (p less than 0.005). Islet cell cytoplasmic antibodies were only detected in diabetes families, since 23% (7/30) of the probands and 7% (2/31) of the siblings were positive and all others negative. Organ-specific autoantibodies were associated with HLA DR3 only in the diabetes families (p less than 0.025) while autoantibody positive members in the control families were associated with HLA B7 (p less than 0.01). This study suggests that childhood IDDM occurs in families with an increased prevalence of organ-specific autoantibodies.

Adolescent↗
PubMed1983

Incidence of infection with hepatitis B virus in 56 patients with haemophilia A 1971-1979.

During each of the four-year periods 1971-1975 and 1975-1979, the annual incidence of hepatitis B infection has been assessed in 56 patients with haemophilia A by measuring plasma HBsAg, anti-HBs and anti-HBc levels. Infection rates of 7% and 9.5% per annum respectively were observed for each four-year period despite the screening of individual blood donations for HBsAg by techniques up to the sensitivity of reversed passive haemagglutination. The highest incidence of seroconversion was amongst severe haemophiliacs many of whom had received treatment predominantly with cryoprecipitate. Of the 16 patients in whom serological evidence of hepatitis B infection was obtained only one had an accompanying clinical episode of hepatitis. We conclude that haemophiliacs are still at high risk of infection by hepatitis B virus despite the screening of individual blood donors for HBsAg.

Adolescent↗
PubMed1983

Inhibition of insulin release after passive transfer of immunoglobulin from insulin-dependent diabetic children to mice.

We used the mouse passive transfer model to test whether islet cell antibodies affect beta-cell function. The immunoglobulin (Ig) fraction of plasma from 5 islet cell surface antibody-positive, newly diagnosed insulin-dependent diabetic children or of a pool of plasma from 12 normal subjects was injected daily (7-16 mg IgG/day) for 14 days into normal immunosuppressed BALB/c mice. Insulin secretory responses in the Ig-injected mice were then examined by perfusing the rodent pancreata in vitro. Insulin release induced by 20 mmol/liter D-glucose during 30 min of stimulation decreased from 900 ng insulin (median; range, 814-1138) from pancreata of mice injected with control Ig to 511 ng (range, 130-786) from pancreata of mice injected with diabetic Ig (P less than 0.003). Both the initial peak and the sustained second phase of glucose-stimulated insulin release were depressed in 4 of the 5 pancreata from mice injected with diabetic Ig. These results indicate that circulating antibodies in diabetic children may alter beta-cell function and possibly contribute to the pathogenesis of insulin-dependent diabetes.

Adolescent↗