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Biomedical subjects

H Burke

Publications and source records attributed to H Burke.

18 recordsLinked to original sources
PubMed2005

Dealing with lead in Broken Hill--trends in blood lead levels in young children 1991-2003.

The objective of the study was to investigate trends in blood lead concentrations in preschool children between 1991 and 2003, as part of the evaluation strategy of a public health lead management program in Broken Hill, Australia. Since 1991, all Broken Hill children aged 1-4 years have been offered at least annual blood lead screening as part of a community-wide lead management program. Recruitment of children was promoted throughout the period using local media and distribution of promotional material from health care centres and preschool, childcare, and educational facilities around the city. Venous blood samples were collected using standard procedures and analyses were subjected to internal and external quality control programs. Because the frequency distribution of blood lead levels are skewed, geometric rather than arithmetic means were used for comparative purposes. Trend analysis was based on age and sex standardised mean blood lead levels. The number of 1- to 4-year-old children screened ranged between 496 and 948 in any one year and response rates varied between 39% and 73%. The age-sex standardised mean blood lead level decreased from 16.3 microg/dL to 7.1 microg/dL between 1991 and 2003. Overall, blood lead levels declined by 56% over 13 years. These reductions were consistently observed irrespective of age or where a child lived in the town. The rate of decline has slowed since 1997. We conclude that substantial progress has been made in dealing with the lead problem in Broken Hill children, although the rate of decline of blood lead levels has slowed. Continued public health action is still needed to bring the proportion of young children with significantly elevated blood lead levels (>15 microg/dL) down from the 2003 figure of 12% to the NHMRC community-based target for lead in young Australians of 5%.

Child, Preschool↗
PubMed2002

Outcome of hip fracture in older Irish women: a 2-year follow-up of subjects in a case-control study.

To assess outcome after hip fracture in older Irish women, 106 consecutive females aged over 50 years admitted to a general hospital with a hip fracture were compared to 89 age- and gender-matched controls from the same catchment area. Interview-based data were collected on socio-demographic factors, mobility and activities of daily living before recruitment and 2 years later. Information was also collected on residence, further falls and fractures and use of health and community support services during the 2-year period. Mortality at 2 years was higher in cases (23.6%) compared to controls (10.1%; P = 0.01). Cases were significantly less mobile and more dependent in the activities of daily living. Of the cases who were community dwellers at baseline, 26.6% were institutionalised at 2 years compared with 9.2% of controls (P = 0.01). During the 2 years cases were significantly more likely to have multiple falls and a further hip or pelvic fracture. Hospital and nursing home admissions and use of physiotherapy, day centre and home help services were also significantly greater among cases. The marked adverse impact of hip fracture reported in this study underlines the importance of public health strategies to prevent these injuries in older people.

Accidental Falls↗
PubMed2001

A pilot study of donepezil for memory problems in epilepsy.

We performed a pilot 3-month, open-label study of 5-10 mg donepezil, an anticholinesterase inhibitor, as treatment for memory problems in people with epilepsy. The Buschke Selective Reminding Test was administered at baseline and after 3 months of donepezil. In 18 completing patients, the total number of words recalled across learning trials was greater on donepezil (P = 0.4). No change was noted in attention, visual sequencing, mental flexibility, psychomotor speed, or reported quality-of-life scores. Mean 3-month seizure frequency at baseline was 2.70 ± 4.60, and during treatment, 3.06 ± 4.52 (P = 0.19, not significant). Two patients experienced increased tonic-clonic seizures. Side effects included diarrhea, stomach cramps, insomnia, depression, and blurred vision. Cholinergic medication is worthy of investigation as treatment for memory problems in people with epilepsy, but attention must be paid to possible exacerbation of seizures.

Journal Article↗
PubMed1999

Methylenetetrahydrofolate reductase thermolabile variant and oral clefts.

Folic acid can prevent neural tube defects; in some cases the mechanism is probably a correction of a metabolic defect caused by thermolabile methylenetetrahydrofolate reductase (MTHFR) found in increased frequency in cases. It is less clear whether folic acid can prevent oral clefts, in part because it is not known whether thermolabile MTHFR is more common in those with oral clefts. This study examined the prevalence of the mutation (677 C-->T) that causes thermolabile MTHFR in subjects with oral clefts from a national Irish support group, and an anonymous control group randomly selected from a neonatal screening program covering all births in Ireland. Eighty-three of 848 control subjects were homozygous (TT) thermolabile MTHFR (9.8%). This defect was almost three times as common in the 27 subjects (25.9%) with isolated cleft palate (odds ratio 3.23, 95% confidence interval 1.32 -7.86, P = 0. 02) and somewhat more common in the 66 subjects with cleft lip with or without cleft palate (15.2%, odds ratio 1.65, 95% confidence interval 0.81-3.35, P = 0.20). When the two groups with different etiologies were combined, the overall odds ratio was 2.06 (95% confidence interval 1.16-3.66, P = 0.02). In the Irish population homozygosity for the common folate-related polymorphism associated with thermolabile MTHFR is significantly more frequent in those with isolated cleft palate, and could be etiologically important. Am. J. Med. Genet. 86:71-74, 1999. Published 1999 Wiley-Liss, Inc.

Child↗
PubMed1999

The "thermolabile" variant of methylenetetrahydrofolate reductase and neural tube defects: An evaluation of genetic risk and the relative importance of the genotypes of the embryo and the mother.

Recent reports have implicated the "thermolabile" (T) variant of methylenetetrahydrofolate reductase (MTHFR) in the causation of folate-dependent neural tube defects (NTDs). We report herein the largest genetic study of NTD cases (n=271) and families (n=218) to date, establishing that, in Ireland, the "TT" genotype is found in 18.8% of cases versus 8.3% of controls (odds ratio 2.57; confidence interval [CI] 1.48-4.45; P=.0005). The maternal and paternal TT genotypes have intermediate frequencies of 13.8% and 11.9%, respectively, indicating that the predominant MTHFR-related genetic effect acts via the TT genotype of the developing embryo. Analysis of the 218 family triads of mother, father, and affected child with log-linear models supports this interpretation, providing significant evidence that the case TT genotype is associated with NTDs (P=.02) but no evidence of a maternal TT genotypic effect (P=. 83). The log-linear model predicted that the risk of NTDs conferred by the case TT genotype is 1.61 (CI 1.06-2.46), consistent with the paramount importance of the case TT genotype in determining risk. There is no compelling evidence for more than a modest additional risk conferred by a maternal TT genotype. These results favor a biological model of MTHFR-related NTD pathogenesis in which suboptimal maternal folate status imposes biochemical stress on the developing embryo, a stress it is ill-equipped to tolerate if it has a TT genotype.

Alleles↗
PubMed1999

Effect of variation in the apo A-IV gene on body mass index and fasting and postprandial lipids in the European Atherosclerosis Research Study II. EARS Group.

The aims of the study were to investigate associations of the apolipoprotein (apo) A-IV polymorphisms Thr347Ser and Gln360His with anthropomorphic measurements and fasting and postprandial lipids in subjects participating in the European Atherosclerosis Research Study II (EARS II). The allelic frequencies of Ser347 and His360 were 0.185 and 0.067, respectively, in the sample as a whole. There were no significant differences in rare allele frequency between cases (offspring of fathers who suffered a myocardial infarction before the age of 55 years) and controls. Control subjects who were carriers of Ser347 had significantly higher body mass indices (BMIs), waist:hip ratios, total and low density lipoprotein cholesterol and triacylglycerol (TG) concentrations (all P < or = 0.02) than control subjects who were non-carriers, but these effects were not seen in the cases. Control subjects who were carriers of His360 had lower BMIs (P = 0.04), cholesterol and TG concentrations (both P < or = 0.07) compared to non-carriers, but these effects were not seen in the cases. After consumption of an oral fat load, carriers of His360 who were most obese (subjects in the third tertile of BMI) had significantly reduced postprandial lipemia (P < 0.03, as assessed by area under the curve).-Fisher, R. M., H. Burke, V. Nicaud, C. Ehnholm, and S. E. Humphries. Effect of variation in the apoA-IV gene on body mass index and fasting and postprandial lipids in the European Atherosclerosis Research Study II.

Adolescent↗
PubMed1998

Low blood folates in NTD pregnancies are only partly explained by thermolabile 5,10-methylenetetrahydrofolate reductase: low folate status alone may be the critical factor.

Thermolabile 5,10-methylenetetrahydrofolate reductase (MTHFR) is the first folate-related variant to be associated with an increased risk of neural tube defects (NTDs). The variant causes high plasma homocysteine levels and reduced red cell folate (RCF) levels, both of which have also been linked to an increased risk of NTDs. We examined the relationship between folate status and presence of the common mutation MTHFR C677T in 82 NTD-affected and 260 control mothers. Homozygosity for the TT genotype was associated with very low folate status among both the cases (n = 13) and the controls (n = 21). However, after exclusion of TT homozygotes, only 10% of the remaining 240 controls had RCF levels less than 200 microg/L compared with 29% of the 69 cases (odds ratio, 3.67; 95% confidence interval, 1.88-7.18; P < 0.001), and those with RCF less than 150 microg/L had eight times higher risk of NTD than subjects with levels over 400 microg/L. Plasma homocysteine levels of non-TT cases were also higher than those of controls (P = 0.047). This study shows that homozygosity for the C677T MTHFR variant cannot account for reduced blood folate levels in many NTD-affected mothers. Thus, a strategy of genetic screening of all childbearing women for this variant would be ineffective as a method of primary prevention of NTDs. The data suggest that low maternal folate status is itself the major determinant of NTD risk, or else that other folate-dependent genetic variants confer risk through the reduction of folate levels. These results emphasize the importance of a food-fortification program as a population strategy for reducing the occurrence of NTDs.

5,10-Methylenetetrahydrofolate Reductase (FADH2)↗
PubMed1995

A genetic defect in 5,10 methylenetetrahydrofolate reductase in neural tube defects.

It is now well-established that folic acid, taken peri-conceptionally, can reduce the risk of neural tube defects (NTDs). Recent work has demonstrated that an abnormality of homocysteine metabolism is a critical factor. The gene for 5,10 methylenetetrahydrofolate reductase, an enzyme important in homocysteine metabolism, was studied in relation to NTDs. To determine the frequency of the allele for the thermolabile form of the reductase, DNA samples were collected from people with NTDs, parents of people with NTDs, and normal controls. Of 82 people with NTDs, 15 (18.3%) were homozygous for the abnormal, thermolabile allele. This was significantly higher (p = 0.01) than the rate of 6.1% in the control population (odds ratio 3.47, 95% CI 1.28-9.41). This is the first specific genetic abnormality to be identified in NTDs. It explains the association between some NTDs and elevated homocysteine, given that the reductase is important in homocysteine metabolism. It also explains how folic acid supplementation prevents some NTDs, by overcoming a partial block in the conversion of 5,10 methylenetetrahydrofolate to 5 methyltetrahydrofolate. Genetic screening could identify women who will require folic acid supplements to reduce their risk of having a child with an NTD.

Case-Control Studies↗
PubMed1993

Maternal plasma folate and vitamin B12 are independent risk factors for neural tube defects.

Blood was taken at the first antenatal clinic from 56,049 pregnant women. Neural tube defect (NTD) pregnancies (81) were compared to controls (247) for plasma vitamin B12 (B12) (ng/l), plasma folate (microgram/l), and red cell folate (RCF) (microgram/l). Median values were significantly different and were, respectively, 243 and 296 (p = 0.001); 3.47 and 4.59 (p = 0.002); and 269 and 338 (p < 0.001). There was a significant correlation between plasma B12 and RCF in cases (r = 0.31, p = 0.004) but not in controls (r = 0.02, p = 0.725). In cases only, multiple regression showed that both plasma B12 and plasma folate influenced the maternal RCF (multiple r = 0.68, p < 0.001). Plasma folate and plasma B12 were independent risk factors for NTDs, suggesting that the enzyme methionine synthase is involved directly or indirectly in the aetiology. The levels of folate and B12 where increased risk occurred were not those usually associated with deficiency, calling for a re-evaluation of their recommended daily allowances. Whether the aetiology is purely nutritional or a metabolic defect, this study suggests that consideration should be given to including B12 as well as folic acid in any programme of supplementation or food fortification to prevent NTDs.

Adult↗
PubMed1983

An evaluation of the reliability and validity of the Functional Assessment Inventory.

The reliability of the Functional Assessment Inventory (FAI) was evaluated using a sample of VA domiciliary and nursing home patients. The interobserver and interrater reliability coefficients of the summary rating scales, based on a single assessment, tended to be higher than their test-retest reliability coefficients, based on two independent assessments separated by a modal four-week interval. Validity coefficients, using the OARS instrument ratings as criteria, also based on two independent assessments several weeks apart, were, on the average, as high as the test-retest reliability coefficients. More specifically, the mental health, physical health, and activities of daily living rating scales, along with the objectively scored Short Portable Mental Status Questionnaire and Short Psychiatric Evaluation Schedule, tended to yield relatively similar scores with repeated measurement, while the social resources and economic resources scales were somewhat less stable, a discrepancy possibly explained by the homogeneous nature of the social and economic status of most of the patients (institutionalized veterans). Thus the reliability and validity of the FAI are satisfactory, but the stability of some of its scales requires further investigation.

Activities of Daily Living↗
PubMed1982

Peak homogeneity determination for the validation of high-performance liquid chromatographic assay methods.

To validate high-performance liquid chromatographic assay procedures with regard to specificity, methods were developed to determine the homogeneity of the chromatographic peaks. These methods employed a rapid-scanning UV-visible spectrophotometer to monitor the chromatographic effluent. The absorption data were processed to nullify the signal due to the drug substances specifically, while allowing the detection of coincident impurities. Results from three model systems indicated the ability of these methods to detect as little as 0.1% of a coincident impurity.

Biotransformation↗
PubMed1981

Prediction of unusual postoperative results by urodynamic testing in benign prostatic hyperplasia.

A survey of preoperative and postoperative urine flow rates, urodynamic data and symptoms in patients undergoing transurethral prostatectomy for benign prostatic hyperplasia indicates that there are certain findings that can help predict early and late postoperative symptoms. Long-term bladder outlet obstruction often is associated with detrusor hyperreflexia. In our series, although all patients had relief of the obstruction when postoperative urine flow rates were measured (p less than 0.005), 28 per cent of the patients who had a hyperreflexic detrusor response had an exacerbation of the symptoms of obstruction 4 weeks postoperatively, while none of the patients with a normal detrusor response noted any increase in symptoms. At 3 months postoperatively all patients still complaining of symptoms demonstrated detrusor hyperreflexia. Patients with detrusor hyperreflexia preoperatively tended to revert to a normal detrusor response after the relief of bladder obstruction. It is concluded that the preoperative finding of detrusor hyperreflexia should alert the surgeon to the possibility of prolonged postoperative symptoms, although the detrusor response eventually will become normal and symptoms will disappear in almost all of these patients.

Aged↗
PubMedDate not supplied

Predictors of first hip fracture and mortality post fracture in older women.

BACKGROUND: Hip fracture causes significant morbidity and mortality in older women. AIM: To document factors contributing to the risk of hip fracture in older women and to assess the effect of hip fracture on subsequent mortality. METHODS: Case-control study of 89 women with hip fracture and 89 controls, with two-year follow-up. Singh index and bone mineral density were calculated. RESULTS: Osteoporotic indices did not differ significantly between cases and controls. Significant predictors of risk were sleeping tablets, perception of health as fair/poor and a lower mental status score. Patients were 3.57 times more likely to die in the first year after fracture, with no difference between the groups in year two. After adjustment, hip fracture did not remain significantly associated with mortality. Inability to walk 100 yards alone prior to fracture and lower social class were significantly associated with mortality at 12 months. Age alone was significantly associated at 12-24 months. CONCLUSIONS: Factors related to falls and fracture may be more discriminatory predictors of hip fracture risk than osteoporosis in older females. Medications for sleep should be prescribed with caution. Hip fracture may have an independent effect on one year mortality, this effect is not seen in the second year.

Accidental Falls↗