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Biomedical subjects

M Mackinnon

Publications and source records attributed to M Mackinnon.

At least 19 recordsLinked to original sources
PubMed2001

High-level chloroquine resistance in Sudanese isolates of Plasmodium falciparum is associated with mutations in the chloroquine resistance transporter gene pfcrt and the multidrug resistance Gene pfmdr1.

Polymorphisms were examined in 2 Plasmodium falciparum genes, as were chloroquine responses of clones and isolates from a village in eastern Sudan. There was a significant association between an allele of the P. falciparum chloroquine resistance transporter gene (pfcrt-T76) and both in vitro and in vivo resistance. There was a less significant association with the multidrug resistance gene pfmdr1-Y86 allele. A significant association between pfmdr1-Y86 and pfcrt-T76 was apparent among resistant isolates, which suggests a joint action of the 2 genes in high-level chloroquine resistance.

ATP-Binding Cassette Transporters↗
PubMed1998

A chloroquine resistance locus in the rodent malaria parasite Plasmodium chabaudi.

We have located a possible chloroquine resistance locus in the genome of the rodent malaria parasite Plasmodium chabaudi. Two genetically distinct clones of the parasite were grown in vivo and allowed to undergo genetic crossing. The clones differed from each other in their susceptibility to chloroquine; AS(3CQ) had been selected for a low level of resistance to the drug whereas AJ is chloroquine-sensitive. Independent recombinant progeny (20) were cloned from the products of two crosses, phenotyped for their susceptibility to chloroquine, and genotyped for their inheritance of 46 chromosome-specific markers. No association was found between chloroquine susceptibility and the inheritance of pcmdr1, the P. chabaudi homologue of the pfmdr1 multi-drug resistance gene of P. falciparum. Also, there was no association between chloroquine susceptibility and the inheritance of a marker linked to a putative chloroquine resistance locus in a P. falciparum cross. However, 16 of the progeny clones showed co-segregation of four linked markers on chromosome 11 with their resistance phenotype. This result suggests that a locus for chloroquine resistance exists on this chromosome in P. chabaudi.

Animals↗
PubMed1998

Has the outcome for extremely low gestational age (ELGA) infants improved following recent advances in neonatal intensive care?

The objectives of this paper are to examine (a) the survival of extremely low-gestational-age (ELGA) infants born at 23-28 weeks' gestational age (GA) and (b) the neurodevelopmental outcome at 18 months corrected age for those born at 23-25 weeks' GA during 1991-1993, when antenatal steroids, surfactant, and dexamethasone for bronchopulmonary dysplasia had become accepted treatments; and to compare with an earlier (1983-1989), previously published large cohort (in a presurfactant era) from our institution. Perinatal and neonatal data on all births delivered at 23-28 weeks' GA at British Columbia's tertiary perinatal center were analyzed for survival rates by GA. Survivors of those born at 23-25 weeks' GA underwent neurodevelopmental assessment at a corrected chronological age of 18 months. The recent cohort (n = 333) of live birth infants, compared to the earlier cohort (n = 911 ) showed a trend toward an overall improved survival to discharge (72 vs. 65%, p = 0.06). Further analysis showed that improved survival was seen only in 26- to 28-week GA infants (86 vs. 76%, p = 0.01), but not in 23- to 25-week GA infants (44 vs. 44%, p = 0.9), even when adjusted for gender or twin births. In addition, the incidence of major impairment at 18 months (36% in both periods) remained high. Reanalysis of 24- to 25-week GA infants again showed no evidence of improved survival (53 vs. 50%) or improved outcome at 18 months (major handicap rate 32%; vs. 34%). Survival rates improved for 26- to 28-week GA infants, but the survival rate and incidence of major impairment had not improved for of 23- to 25-week GA infants.

Age Factors↗
PubMed1998

A rank-based nonparametric method for mapping quantitative trait loci in outbred half-sib pedigrees: application to milk production in a granddaughter design.

We describe the development of a multipoint nonparametric quantitative trait loci mapping method based on the Wilcoxon rank-sum test applicable to outbred half-sib pedigrees. The method has been evaluated on a simulated dataset and its efficiency compared with interval mapping by using regression. It was shown that the rank-based approach is slightly inferior to regression when the residual variance is homoscedastic normal; however, in three out of four other scenarios envisaged, i.e., residual variance heteroscedastic normal, homoscedastic skewed, and homoscedastic positively kurtosed, the latter outperforms the former one. Both methods were applied to a real data set analyzing the effect of bovine chromosome 6 on milk yield and composition by using a 125-cM map comprising 15 microsatellites and a granddaughter design counting 1158 Holstein-Friesian sires.

Animals↗
PubMed1998

Broadband multimedia for education.

Over the next five to ten years the accelerating development of computing and broadband networks will lead to a revolution in the ways in which health care is delivered. Patients will spend less time in the great institutions of the tertiary hospitals and the illnesses taking them there will assume a different pattern. The new information technologies will foster the emergence of general practices with a new emphasis on keeping patients in their communities for medical management. Knowledge exchange and delivery--to both patient and practitioner--will therefore become an increasingly important component of the health-care system in the next millennium.

Australia↗
PubMed1995

A long-term study of the interaction between iron and alcohol in an animal model of iron overload.

BACKGROUND/AIMS: The hypothesis that chronic alcohol ingestion potentiates iron-associated liver injury was investigated in the 'carbonyl iron-overload rat model'. METHODS: Newborn male and female Wistar-Furth rats (seven per group) were used to investigate iron-alcohol interaction over a 26-week period. Groups 1 and 2 were iron loaded from birth, while the others received normal diet. At 10 weeks all rats commenced Lieber-DeCarli liquid diet; additional treatments were: group 1 6 g carbonyl iron/1000 ml diet plus alcohol; group 2 carbonyl iron in the liquid diet; group 3 alcohol in the liquid diet; group 4, the controls, received liquid diet only. RESULTS: This study confirmed our previous observation that iron-loading from birth resulted in grade III-IV siderosis, in both male and female rats, and caused fibrosis associated with periportal macrophages. Alcohol-feeding, in addition to iron-feeding for 26 weeks significantly lowered the hepatic iron concentration in both male and female rats compared to those fed iron only (p < 0.05). Alcohol feeding did increase hepatic fibrosis in the iron-loaded animals. However, serum alanine aminotransferase activity was significantly higher in the iron-alcohol group than in the other groups (p < 0.05). CONCLUSIONS: Thus, contrary to expectation, chronic alcohol feeding failed to potentiate hepatic fibrosis in iron-overloaded rats, although there was rather more hepatocyte necrosis, and the serum alanine aminotransferase activity was significantly higher in the iron-alcohol group than in the other groups.

Alcoholism↗
PubMed1995

Mapping quantitative trait loci controlling milk production in dairy cattle by exploiting progeny testing.

We have exploited "progeny testing" to map quantitative trait loci (QTL) underlying the genetic variation of milk production in a selected dairy cattle population. A total of 1,518 sires, with progeny tests based on the milking performances of > 150,000 daughters jointly, was genotyped for 159 autosomal microsatellites bracketing 1645 centimorgan or approximately two thirds of the bovine genome. Using a maximum likelihood multilocus linkage analysis accounting for variance heterogeneity of the phenotypes, we identified five chromosomes giving very strong evidence (LOD score > or = 3) for the presence of a QTL controlling milk production: chromosomes 1, 6, 9, 10 and 20. These findings demonstrate that loci with considerable effects on milk production are still segregating in highly selected populations and pave the way toward marker-assisted selection in dairy cattle breeding.

Animals↗
PubMed1995

The life-expectancy of persons with cerebral palsy.

Survival rates for persons with cerebral palsy were calculated using information from a population-based registry which has been collecting data since 1952. The 30-year survival rate approximates 87 per cent. Adverse factors affecting survival are the type of cerebral palsy (spastic quadriplegia having the worst prognosis), epilepsy and severe or profound mental retardation. The length of time over which the data were collected precludes estimating survival time beyond 30 years.

Adolescent↗
PubMed1995

Standardization of flow cytometric crossmatch (FCXM) for investigation of unexplained habitual abortion.

PROBLEM: To define a positive flow cytometric crossmatch (FCXM), in terms of channel shift, for maternal IgG and IgM (n = 28) against paternal T and B lymphocytes. METHOD: A reference range study. Mononuclear cells were obtained from 28 healthy volunteers using density gradient separation of heparinized blood, followed by pre-incubation with goat immunoglobulin. A total of twelve tubes were prepared for each volunteer. Primary incubation was with negative control serum, positive control sera (either IgG or IgM) and individual AB sera. Secondary incubation was with four combinations of fluorochromes: CD3 PE/IgG-Fc F(ab')2FITC, CD3 PE/IgM F(ab')2FITC, CD20 PE/IgG-Fc F(ab')2FITC and CD20 PE/IgM F(ab')2FITC. The cells were then analyzed with an EPICS Profile flow cytometer, using 256-channels and a four decade log scale. RESULTS: The linear mean channel fluorescence of the negative control serum was subtracted from the individual AB sera (channel shift) for each of the four combinations of fluorochromes. By determining the 95% one-sided upper reference limits of the negative control serum for each of the four trimmed data sets, we clinically defined a positive FCXM for bound IgG or IgM to T lymphocytes as a shift of 10 or more channels, and for bound IgG or IgM to B lymphocytes as a shift of 25 or more channels, above the linear mean channel shift of the negative control serum. CONCLUSION: Positive FCXMs were defined for maternal IgG and IgM against T and B lymphocytes, in terms of channel shift above the linear mean channel fluorescence of the negative control serum. By standardizing the dual-color FCXM methodology, the clinical significance of alloantibodies in the maintenance of pregnancy could be addressed in a collaborative manner.

Abortion, Habitual↗
PubMed1995

Iron overload facilitates hepatic fibrosis in the rat alcohol/low-dose carbon tetrachloride model.

The role of iron deposition in initiating hepatic fibrosis in iron overload disorders is not clearly established, and it is becoming increasingly recognized that iron may be interacting with other potential liver-damaging agents. The authors therefore examined the interplay of iron and alcohol in rats administered subtoxic doses of carbon tetrachloride (CCl4) vapor at 20 ppm in customized chambers. At birth, the offspring of seven pregnant Porton rats were divided into two groups: one group was fed a normal rat chow diet and the other a diet supplemented with 3% (w/w) carbonyl iron for 10 weeks after weaning. In this latter group, the mothers were fed an iron supplement while breastfeeding. At 10 weeks, the animals from the first group (normal chow) were divided into two groups of six animals and fed a Lieber-DeCarli liquid diet with daily exposure to CCl4 vapor: group 1, liquid diet+CCl4; group 2, liquid diet+alcohol 150 kcal/l+CCl4. The animals from the second iron-supplemented group were divided into two groups of six animals and fed a liquid diet with 3% (w/v) carbonyl iron and exposed to CCl4 vapor for 10 weeks: group 3, liquid diet+iron+CCl4; group 4, liquid diet+iron+alcohol supplement+CCl4. Two animals from each group of six had a liver biopsy at 4, 6, and 8 weeks, and all animals were killed after 10 weeks of CCl4 exposure. After the first 10-week iron loading period, the rats fed the carbonyl iron-supplemented diet had a 10-fold elevation in hepatic iron concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Predictors of success of reversal of sterilization.

OBJECTIVE: To determine the prognostic variables effecting the successful pregnancy outcome of reversal of sterilization. DESIGN: Demographic and clinical history data were collected prospectively. SETTING: Division of Infertility and Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, Canada. PATIENTS AND INTERVENTION: Between 1981 and 1992, 217 consecutively referred patients underwent reversal of sterilization by a single surgeon using microsurgical techniques. MAIN OUTCOME MEASURES: Prognostic variables associated with success were examined using logistic regression and expressed as odds ratios with corresponding 95% confidence intervals. RESULTS: Age at reversal was a significant factor with the odds of a successful outcome for those < or = 35 years compared with those > 35 years being 2.3 with a 95% confidence interval of 1.3 to 4.1. There was some evidence that average tubal length as categorized in 2-cm intervals was a significant prognostic factor with the odds of a successful outcome for those with an average length of > 4 cm to those < or = 4 cm being 5.3 with a 95% confidence interval of 1.4 to 20.0. CONCLUSIONS: Nonsubjective analysis of the prognostic variables of reversal of sterilization associates only age and tubal length of > 4 cm with intrauterine pregnancy.

Adult↗
PubMed1994

Perinatal outcomes of a large cohort of extremely low gestational age infants (twenty-three to twenty-eight completed weeks of gestation).

OBJECTIVES: To determine gestational age (GA)-specific mortality rates; the effects of GA, birth weight, sex, and multiple gestation on mortality rates; short-term morbidity for infants born at 23 to 28 weeks GA; and impairment rates at a corrected chronologic age of 18 months for those born at 23 to 25 weeks GA. METHODS: A data base analysis was performed with a linked obstetric and a neonatal database. GA was determined by obstetric data and confirmed by early ultrasonography (available in 88%) on all births < 30 weeks GA at British Columbia's tertiary perinatal center from 1983 to 1989. RESULTS: Of 1024 births occurring between 23 and 28 weeks GA, 911 were live born. The mortality rate decreased with increasing GA: 84% at 23 weeks; 57% at 24 weeks; 45% at 25 weeks; 37% at 26 weeks; 23% at 27 weeks; and 13% at 28 weeks GA. For each GA, mortality rate versus birth weight plots showed a decreasing mortality rate with increasing birth weight, except for infants who were large for GA. Male infants had a higher mortality rate than female infants (odds ratio, 1.8; confidence interval, 1.4 to 2.5). Twins fared worse than singletons with a decreasing effect from 24 weeks GA (odds ratio, 10.3) to no effect at 28 weeks GA. The median number of days supported by mechanical ventilation and the length of stay in the neonatal intensive care unit decreased markedly with increasing GA. Eighteen-month outcome of survivors between 23 and 25 weeks GA with 93% follow-up rate revealed an overall impairment rate of 36%, but 6 of the 9 surviving 23-week infants had major impairments. CONCLUSIONS: The GA-specific perinatal outcome results of this large cohort provide information to assist in perinatal management decision making and for counseling parents prenatally.

Adolescent↗
PubMed1994

Screening for genetic haemochromatosis in a rheumatology clinic.

BACKGROUND: Recent data indicate that the prevalence of genetic haemochromatosis (GH) is greater than previously recognised and suggest that this disease is underdiagnosed. AIMS: To determine the prevalence of GH in rheumatology clinic population. METHODS: Over a 12 month period 339 consecutive patients, mean age 67.0 years, attending a rheumatology clinic were screened for iron overload. RESULTS: Twenty three patients had elevated initial screening tests (transferrin saturation [Tf%] > 55%; ferritin > 500 micrograms/L). Repeat fasting Tf% and ferritin concentrations were obtained in 20 of these patients. Twelve patients had persistently elevated results, and of these patients four had liver biopsy tissue hepatic iron indices consistent with GH. One patient in the group had the diagnosis established by liver biopsy just before the screening commenced. Thus, the prevalence of GH in this population was 1.5%--five times that anticipated for the general population. Three of the patients with GH presented with an arthropathy which was not characteristic of the disease. The increased prevalence of GH in this group of patients with peripheral arthropathy provides an excellent justification for the routine screening of patients with peripheral arthritis for the exclusion of iron overload.

Aged↗
PubMed1994

Omeprazole v ranitidine for prevention of relapse in reflux oesophagitis. A controlled double blind trial of their efficacy and safety.

The aim of this study was to compare recurrence rates of reflux oesophagitis (after endoscopic healing with omeprazole) over a 12 month period of randomised, double blind, maintenance treatment with either daily omeprazole (20 mg every morning; n = 53), weekend omeprazole (20 mg on three consecutive days a week, n = 55) or daily ranitidine (150 mg twice daily, n = 51). Patients were assessed for relapse by endoscopy (with gastric biopsy) at six and 12 months, or in the event of symptomatic recurrence, and serum gastrin was monitored. At 12 months, the estimated proportions of patients in remission (actuarial life table method) were 89% when receiving daily omeprazole compared with 32% when receiving weekend omeprazole (difference 57%, p < 0.001, 95% confidence intervals: 42% to 71%) and 25% when receiving daily ranitidine (difference 64%, p < 0.001, 95% confidence intervals: 50% to 78%). Median gastrin concentrations increased slightly during the healing phase, but remained within the normal range and did not change during maintenance treatment. No significant pathological findings were noted, and no adverse events were attributable to the study treatments. In conclusion, for patients who respond favourably to acute treatment with omeprazole 20 mg every morning, the drug is a safe and highly effective maintenance treatment for preventing relapse of reflux oesophagitis and its associated symptoms over 12 months. By contrast, weekend omeprazole and daily ranitidine were ineffective.

Adolescent↗
PubMed1994

Exogenous gonadotropin therapy in World Health Organization groups I and II ovulatory disorders.

OBJECTIVE: To analyze cumulative conception rates and the prognostic factors influencing them during exogenous human menopausal gonadotropin (hMG) therapy for World Health Organization (WHO) group I or II ovulatory disorders. METHODS: A retrospective review was conducted of 468 treatment cycles in 146 women with ovulatory disorders refractory to conventional therapy. Cumulative conception rates were calculated, and the effects of diagnostic group, age, gravidity, and duration of infertility were examined using the Cox proportional hazards model. RESULTS: The cumulative proportion pregnant following six hMG cycles in WHO group I (0.89) was significantly greater than in the hyperandrogenic subgroup of WHO group II (0.30) (95% confidence interval [CI] 0.2-0.7, P = .006) or the luteal phase defect subgroup (0.35) (95% CI 0.07-0.6, P = .02). Conception rates in WHO group I did not differ significantly from those in the normoandrogenic oligo-ovulatory subgroup of WHO group II (0.63) (95% CI 0.3-1.3, P = .6). Conception rates were not influenced by duration of infertility or primary versus secondary infertility. Women 35 years or older had significantly lower conception rates than those aged 27 years or less (P = .04, hazard ratio 0.3, 95% CI 0.1-0.8). CONCLUSIONS: Cumulative conception rates following exogenous gonadotropin therapy for women with refractory ovulatory disorders were both diagnosis- and age-dependent. Treatment with hMG approximated or surpassed normal fertility rates in women with WHO group I and normoandrogenic WHO group II oligo-ovulation, but was significantly less successful at correcting the underlying defect in women with hyperandrogenic anovulation and luteal phase defects.

Adult↗