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Biomedical subjects

W J Hensley

Publications and source records attributed to W J Hensley.

At least 19 recordsLinked to original sources

Lipoproteins, atherogenicity, age and risk of myocardial infarction.

OBJECTIVE: To perform basic statistical analysis of laboratory lipoprotein data, i.e. the measures of very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL), to assist in their interpretation. In particular, to find any difference in male and female data that might explain the known difference in atherogenic susceptibility between the sexes. METHOD: The study subjects were patients of doctors in city and country New South Wales. Statistical methodology to find the inter-relations of the lipoproteins was the construction of the matrix of correlation, then by matrix algebra to display the independent trends in the data. RESULTS AND CONCLUSIONS: The findings have been an atherogenicity function involving LDL and HDL and a risk function of myocardial infarction (MI) involving LDL, HDL and age, confirmed by reference to the age and sex incidence of MI in the Australian population. The principal conclusion is a simple mathematical model of the incidence of MI. IMPLICATIONS: The means given for identification of at-risk individuals before symptoms appear, also the means given of lowering whole population risk of MI by health education and lifestyle change with increased longevity for all. These concepts call for a prospective trial.

Adult↗

Comparability of lipoprotein measurements, total:HDL cholesterol ratio and other coronary risk functions within and between laboratories in Australia.

We assessed the intralaboratory imprecision and interlaboratory comparability of lipoprotein measurements and related cardiovascular risk functions such as the total to high density lipoprotein cholesterol (TC:HDL) ratio. Analysis of 5 separate plasma pools was carried out in 4 laboratories which regularly perform lipoprotein testing. We also performed a retrospective audit on RCPA-AACB Quality Assurance Programme data from 134 laboratories participating in the Special Lipid Programme in 1991. Intralaboratory imprecision and interlaboratory comparability are reported as coefficient of variation (cv) and its 95% confidence limit. For the national data, we calculated the percentage of laboratories within specified ranges (+/- 3, 5 or 10%) about the national mean (or median) for a given level of each analyte. Intralaboratory imprecision and interlaboratory comparability amongst the 4 laboratories were close to, or within recommended limits for, TC, TG and HDL, but the interlaboratory comparability of LDL and coronary risk functions exceeded these limits. On a national level, interlaboratory comparability of TC:HDL was within +/- 5% for only 43% of laboratories, and even fewer (26%) were within this range at higher values of the ratio. We conclude that it is not possible to recommend the use of coronary risk functions at present because of sub-optimal interlaboratory comparability. Even if measures are introduced to overcome this problem, coronary risk functions may over-simplify coronary vascular disease risk in a variety of clinical situations.

Australia↗

Postprandial changes in apolipoprotein(a) concentration of triglyceride-rich lipoproteins can be reproduced by in vitro incubation: implications for underlying mechanism.

We investigated the reciprocal changes in apolipoprotein(a) concentration in the lipoprotein of d > 1.006 and the triglyceride-rich lipoprotein (TRL) fractions of plasma which occur in vivo following fat ingestion. Twenty fasting subjects were studied before and 4 h after a fat-rich meal. In 75% of cases, in vitro incubation of the postprandial (4-h) TRL with autologous fasting (0-h) lipoproteins of d > 1.006 resulted in further substantial (> 5% total) reciprocal changes in apo(a) concentration of the 2 fractions. The increase in re-isolated postprandial TRL apo(a) was 25.1% +/- 5.1% of the total apo(a), compared to the insignificant increase (0.1% +/- 0.1%) in re-isolated fasting TRL. Most of the further increase in 4-h TRL apo(a) (94% +/- 4%) could be achieved by incubation with the corresponding 4-h chylomicron fraction (CM) alone. The re-isolated 4-h TRL apo(a) concentration correlated positively with 4-h plasma TG concentration (r = 0.65, P < 0.01) and other indices of postprandial lipaemia. In vitro incubation of pooled serum lipoproteins of d > 1.006 with serial dilutions of nascent CM obtained from chylous ascitic fluid revealed that the reciprocal changes in apo(a) concentration exhibit a curvilinear relationship with the concentration of CM triglyceride which plateaued round 7 mmol/l in this instance. We conclude that the reciprocal changes in apo(a) concentration between TRL and lipoproteins of d > 1.006 which occur in the postprandial phase are quantitatively significant and largely represent a redistribution process rather than de novo synthesis because they can be reproduced by in vitro incubation.

Adult↗

Plasma lipoprotein distribution of apolipoprotein(a) in the fed and fasted states.

In order to quantitate the contribution of triglyceride-rich lipoprotein (TRL) apolipoprotein(a) to total plasma apo(a) concentration in the fed and fasted states, we have studied a group of 20 male subjects (age 49 +/- 3 years) with fasting apo(a) concentrations varying from 39 to 1385 U/l. After a 12-h overnight fast, each subject was given a fat-rich meal (1 g fat/kg body weight) and venous blood samples were obtained at hourly intervals for 10 h. TRL were isolated from bihourly plasma samples by ultracentrifugation (d less than 1.006 g/ml) and apo(a) was measured by radioimmunoassay. Total plasma apo(a) concentration did not change after the meal. However, TRL apo(a) increased significantly (0 h: 3 +/- 1, 4 h: 30 +/- 7 U/l; p less than 0.001) and 'd greater than 1.006' apo(a) decreased (0 h: 267 +/- 56, 4 h: 231 +/- 50 U/l; P less than 0.05). Similar postprandial changes were observed in apoB concentration (TRL apo B at 0 h: 10.3 +/- 1.5, 4 h: 13.6 +/- 1.7 g/l, P less than 0.001, 'd greater than 1.006' apoB at 0 h: 118 +/- 7, 4 h: 110 +/- 7 g/l, P less than 0.001). In the fasted state 2.0 +/- 1.0% and in the fed state (4 h postprandially) 16.0 +/- 4.6% of total plasma apo(a) was found in the TRL fraction. Eleven subjects had less than 10% of total apo(a) in TRL, 5 had 25% or more apo(a) in TRL in the fed state. Postprandial increase in TRL apo(a) was significantly correlated (r = 0.75, P less than 0.001) with increase in plasma triglycerides. TRL apo(a) concentration in the fed state was not correlated with total fasting cholesterol, triglyceride, apo(a) or HDL cholesterol concentration. We conclude that in some individuals, TRL apo(a) makes a significant contribution to total plasma apo(a) concentration in the fed state.

Adult↗

Benign prostatic hyperplasia--video image analysis and its relationship to androgen and epidermal growth factor receptor expression.

Androgens are essential for the development and maintenance of the prostate. However, prostatic growth may be mediated by epidermal growth factor (EGF) and the expression of the EGF receptor (EGFR) may be influenced by the androgenic milieu. We have characterized the expression of cytosolic androgen receptor (ARc), nuclear salt extractable androgen receptor (ARn) and EGFR in 89 consecutive cases of benign prostatic hyperplasia, 84 of which were treated by transurethral prostatic resections. Image analysis morphometry was performed on the histological sections to determine the epithelial content of the gland. Our results indicate that there is a vast heterogeneity of receptor expression in benign prostatic hyperplasia. Expression of ARc ranged from zero to 1312 fmol/gm. tissue (mean +/- SD 265 +/- 290), ARn ranged from zero to 531 fmol/gm. tissue (mean +/- SD 145 +/- 98) and EGFR ranged from zero to 316 fmol/gm. tissue (mean +/- SD 121 +/- 76). A statistically significant association was found between expression of ARn and EGFR, and these were both significantly correlated with the epithelial content of the gland.

Cell Nucleus↗

Assessment of HIV status using the polymerase chain reaction in antibody-positive patients and high-risk antibody-negative haemophiliacs.

The polymerase chain reaction (PCR) was used to identify the presence of DNA sequences homologous to HIV-1 in the buffy-coat leukocytes of antibody-positive and antibody-negative individuals in a haemophiliac population. The presence of HIV sequences was demonstrated in all of the antibody-positive haemophiliacs with the exception of one patient who was repeatedly negative. None of the seronegative haemophiliacs gave an overall positive result, although there were clear differences between this population and the negative controls who were examined. We conclude that, in our hands, PCR represents a reliable test which represents a useful diagnostic advance in HIV medicine.

Base Sequence↗

The effects of dietary n - 3 fatty acid in animal models of type 1 and type 2 diabetes.

We studied the incorporation of dietary n - 3 fatty acids from marine oils into red cell membranes, using animal models of type 1 diabetes (streptozotocin-treated Wistar rats) and type 2 diabetes (gold-thioglucose-injected CBA/T6 mice). In type 1 diabetic rats, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were higher following marine oil supplementation, and the increase in EPA was significantly greater than in non-diabetic animals (3.4 +/- 1.4% vs. 0.8 +/- 1.6%). Marine oil supplementation also resulted in higher levels of EPA and DHA in mice, but the increases were quantitatively similar with and without type 2 diabetes. Improvement in glycosylated haemoglobin following n - 3 fatty acid feeding was only found in type 2 diabetes (6.5 +/- 2.9% vs. 9.5 +/- 1.2%). This was associated with a higher plasma insulin concentration (170 +/- 40 vs. 136 +/- 41 mU/ml). The theory that n - 3 fatty acids improve insulin sensitivity would have predicted a decrease in plasma insulin levels. Our results suggest that n - 3 fatty acids may modify insulin secretion.

Animals↗

Randomised controlled trial of recombinant human interferon -alpha A for chronic active hepatitis B.

The efficacy of interferon treatment for Australian patients with chronic active hepatitis B (CAH-B) was assessed by a three-centre randomised controlled trial in Sydney and Brisbane. Thirty patients (29 with histologically-proven CAH-B with and without cirrhosis and one with chronic persistent hepatitis) were allocated to receive either thrice weekly intramuscular injections of recombinant human leucocyte interferon -alpha A (either 2.5, 5.0 or 10.0 million units/m2) for six months followed by 12 months of observation, or to be observed for 18 months without active treatment. Three of 23 treated patients but none of seven controls underwent clinical, biochemical and histological resolution of their disease with loss of HBsAg, HBeAg and HBV-DNA from serum. An additional six treated and two control patients underwent a sustained partial remission of their disease. This was characterised by resolution of symptoms and serum aminotransferase abnormalities in association with seroconversion from HBeAg positive to negative, loss of HBV-DNA from serum but persistent hepatitis B surface antigenaemia. In such patients, there was significant improvement in histological appearances but some necroinflammatory activity remained and fibrosis was unchanged. Although total response rates were similar in treated and control subjects, they appeared to occur earlier after interferon treatment. Treatment with interferon was associated with predictable but minor side effects that usually did not necessitate dose reduction and rarely compromised the patient's life style. Interferon is thus a feasible treatment for CAH-B. Complete responses occurred only in treated patients and partial responses appeared to occur earlier in treated than in untreated patients. However, differences in the partial response rate at 18 months were not significant and seroconversion from HBeAg positive to negative was not associated with complete histological resolution of disease activity. Hence, while interferon is a promising agent for treatment of CAH-B, efforts must continue to define more optimal treatment regimes and to identify those patients most likely to respond to this agent.

Adult↗

Diagnostic value of cerebrospinal fluid myelin basic protein in patients with neurological illness.

The levels of myelin basic protein (MBP) in the cerebrospinal fluid (CSF) have been evaluated as a method of detecting central nervous system (CNS) demyelination. MBP levels were measured in the CSF of 129 patients with neurological illnesses of whom 26 had a demyelinating illness. High levels of MBP were found in 81% of patients with recent episodes of demyelination but were not seen in patients with multiple sclerosis that was clinically stable or in remission. Patients with CNS trauma also had high levels of MBP in their CSF. The detection of a high level of MBP in CSF may be useful in the diagnosis of acute CNS demyelination but the finding is not specific for multiple sclerosis.

Demyelinating Diseases↗

An exhaustive tree-searching algorithm for high-resolution computer-assisted nucleotide sequence analysis.

A new computer search strategy has been devised for high-resolution nucleotide sequence analysis. The strategy differs from those used by earlier sequence analysing programs in that it is exhaustive and capable of detecting all possible homologies and other types of relationships between or within sequences irrespective of the pattern of matches and mismatches encountered. The implementation of this strategy into a working algorithm is described.

Algorithms↗

The SEQANAL and SEQTALK programs: a new method of access to high-resolution nucleotide sequence comparison and analysis programs from a remote laboratory mini- or microcomputer.

A new method of access has been devised for biologists requiring the use of computer programs offering high-resolution analysis and comparison of nucleotide sequence data. The strategy involves the development of a pair of computer programs, called SEQANAL and SEQTALK, designed to operate in tandem. SEQANAL is a large and complex program intended to be used to discover regions of internal repeats and dyad symmetries within one sequence, or regions of homology, complementarity or optimal alignment between two sequences. Three algorithms are supported: those of Staden (1977, 1978); of Korn et al. (1977); Queen and Korn (1980); and the newly-described exhaustive tree-searching algorithm of Burnett et al. (1985, 1986). The SEQTALK program is a small, portable, interactive, front-end program with which the user can specify the instructions to control the SEQANAL program. Together, the SEQANAL and SEQTALK programs permit analyses to be performed at a remote facility on a mainframe computer under the complete control of a distant user equipped with minimal computing facilities, and without needing networking facilities.

Algorithms↗

Thiamine deficiency--a neglected problem of infants and mothers--possible relationships to sudden infant death syndrome.

An unexpectedly high incidence of biochemical thiamine deficiency (erythrocyte transketolase) was found in groups of mothers and infants, selected for apparent health from a westernized Caucasian community in Australia. Deficiency was common in mothers at term but not their infants, and in apparently healthy older infants but not their mothers. These findings can be explained by preferential delivery of thiamine to the fetus, at the expense of the pregnant mother; after delivery the mother recovers, and the infant becomes depleted. The incidence of thiamine deficiency was high in 'near-miss' sudden infant death syndrome (SIDS) infants and their mothers, and in siblings of SIDS. The thiamine deficient infants had a high familial incidence of SIDS deaths. These 'high risk families' might reflect poor nutrition or genetic defects of thiamine uptake and metabolism. Since apparently thriving infants with thiamine deficiency can sometimes die unexpectedly, thiamine status deserves more attention in clinical practice and research.

Adult↗

Can potentially infectious specimens containing hepatitis B virus be identified on the basis of their biochemical profile?

The potential infectivity of 1129 randomly selected plasma specimens was directly assayed by hepatitis B virus (HBV) DNA dot-hybridization. Presence or absence of HBV was then correlated with a biochemical profile of 20 common analytes obtained on these same specimens. We found that potentially infectious specimens could not be identified on the basis of any combination of simple biochemical tests; indeed, the infectious specimens were more "normal" in some tests of liver function than were the non-infectious specimens.

Blood Specimen Collection↗