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M J West

Publications and source records attributed to M J West.

At least 73 records · Page 4Linked to original sources
PubMed1994

Renin and angiotensin-converting enzyme genotypes in patients with essential hypertension and left ventricular hypertrophy.

1. The associations between left ventricular hypertrophy (LVH) and specific alleles of the renin and angiotensin-converting enzyme (ACE) genes were studied in patients with essential hypertension and normal blood pressure. 2. LVH was present in 42% of those with essential hypertension (n = 72) and 17% of those with normal blood pressure (n = 44). 3. The frequency of each renin allele was the same in hypertensive and in normotensive patients. Renin allele frequencies were also the same for those with LVH and those with normal cardiac mass. When only hypertensives were considered, renin alleles were in the same proportion for the groups with and without LVH. Similarly, ACE alleles were not associated with essential hypertension nor with elevated cardiac mass. 4. We conclude that, in this population, variations in the renin or ACE genes do not contribute significantly to the development of LVH or to essential hypertension.

Alleles↗
PubMed1994

Felodipine, metoprolol and their combination compared with placebo in isolated systolic hypertension in the elderly.

This study compared with placebo the efficacy and tolerability of optimised doses of felodipine 5-20 mg daily, metoprolol 50-200 mg daily and their combination in subjects 60 years or over with isolated systolic hypertension. The study employed a randomised double-blind crossover design with allocation of treatment order within subjects by Latin squares. For each subject, after a single-blind run-in placebo phase, there were four randomised treatment phases each of six weeks duration, with a dose titration step at three weeks if necessary. Twenty-eight subjects entered the randomised phases of the study and twenty-one completed all four phases--13 male, 8 female (ages: median 71, range 59-85 years). At the end of both the felodipine and metoprolol phases systolic and diastolic pressure were reduced at 2 hours postdose compared with the placebo phase (p < 0.001), the blood pressure reduction with felodipine (-40/-20 mmHg) being greater than that with metoprolol (-15/-9 mmHg) (p < 0.01). Immediately predose (12 hours postdose) there was a persisting reduction of supine systolic blood pressure (-17 mmHg) with felodipine (p < 0.001), but there was no significant effect of metoprolol. At both measurement times the two drugs when in combination had an additive effect on blood pressure. There was a 20% increase in reported symptoms during each of the active treatment phases. Four subjects withdrew during the randomised phases because of probable drug-related adverse events and six subjects required dosage reductions during the felodipine or combination phases.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Mono- and combination therapy with felodipine or enalapril in elderly patients with systolic hypertension.

Using a randomised double-blind crossover design with Latin square allocation of treatments in 20 subjects (7 male, 13 female-ages: 61-87 years) with systolic hypertension, we investigated the efficacy and tolerability of once daily felodipine (extended release) 5-20 mg, enalapril 5-20 mg and their combination compared with placebo in four treatment phases each of 6 weeks duration. During each phase, doses were titrated to achieve a predose clinic supine systolic blood pressure of 140 mmHg or to a predetermined maximum dose. In both the felodipine and combination phases, predose supine and standing systolic and diastolic pressures were significantly reduced compared with the placebo phase (decrease in supine pressure: -13/-5 and -18/-7, respectively). Only predose supine diastolic pressure was significantly reduced (-3 mmHg) compared to placebo in the enalapril phase. In combination the effects of the two drugs on predose blood pressure were additive. There was a 40-60% increase in reported symptoms in the felodipine and combination phases compared with the placebo and enalapril phases. Thus, in elderly subjects with systolic hypertension, felodipine effectively reduces blood pressure throughout the dose interval but with vasodilator adverse effects. In contrast, enalapril is well tolerated but is less effective in reducing blood pressure throughout the whole dose interval.

Aged↗
PubMed1993

Angiotensin-converting enzyme and regulation of blood pressure in a large Australian family.

1. Animal studies have implicated the angiotensin-converting enzyme (ACE) gene as an inherited risk factor contributing towards elevation of blood pressure. 2. A polymorphism of the ACE gene, involving the presence or absence of a 287 base pair (bp) segment within the gene region, was assessed for association with high blood pressure in a large, multigeneration Australian family. The association of these alleles with hypertension in unrelated individuals was also examined. 3. There was no evidence to link the ACE gene and high blood pressure in the large family. Similarly, there was no significant association between this gene and high blood pressure in the population tested. As has been reported previously, plasma levels of the enzyme were associated with genotype. These results suggest that this gene is unlikely to be a major risk factor for hypertension in this group.

Adult↗
PubMed1993

Structural influences on resistance in the hindlimb vascular bed of the renal hypertensive rabbit.

1. The contribution of arteriolar structural change to hindlimb vascular resistance was examined in the renal wrap hypertensive rabbit. 2. Haemodynamic variables were recorded at rest and after maximal vascular dilation using sodium nitroprusside and peripheral autonomic effector blockade. In the same animals at the end of experiments, morphometric measurements of hindlimb muscle arterioles were made. 3. Mean arterial pressure (MAP) and hindlimb vascular resistance were elevated in hypertensive animals compared with normotensive animals at rest and after maximal dilation. 4. Lumen area and lumen diameter were reduced whereas wall area and wall area to lumen area ratio were increased in hypertensive animals compared with normotensive animals. 5. In the renal wrap model of hypertension, the reduction in lumen area of arterioles, < 200 microns in diameter, is sufficient to explain the increase in haemodynamic resistance.

Animals↗
PubMed1992

Polymorphisms of candidate genes in essential hypertension.

1. Family and population studies have reported that blood pressure has a heritability of 30-50%, but simple genetic models do not readily explain the patterns of inheritance of hypertension. 2. Restriction fragment length polymorphisms were used to study allele frequencies of a selection of candidate genes that may be important in determining the genetic component of hypertension. These included the genes for renin, haptoglobin, neuropeptide Y and cardiac myosin beta heavy chain. 3. There was no significant association between alleles at any of these loci and the presence of hypertension in this population, suggesting that the contribution of variation at these loci to the genetic component of the variance in hypertension may be quite small.

Alleles↗
PubMed1991

Unbiased stereological estimation of the total number of neurons in thesubdivisions of the rat hippocampus using the optical fractionator.

A stereological method for obtaining estimates of the total number of neurons in five major subdivisions of the rat hippocampus is described. The new method, the optical fractionator, combines two recent developments in stereology: a three-dimensional probe for counting neuronal nuclei, the optical disector, and a systematic uniform sampling scheme, the fractionator. The optical disector results in unbiased estimates of neuron number, i.e., estimates that are free of assumptions about neuron size and shape, are unaffected by lost caps and overprojection, and approach the true number of neurons in an unlimited manner as the number of samples is increased. The fractionator involves sampling a known fraction of a structural component. In the case of neuron number, a zero dimensional quantity, it provides estimates that are unaffected by shrinkage before, during, and after processing of the tissue. Because the fractionator involves systematic sampling, it also results in highly efficient estimates. Typically only 100-200 neurons must be counted in an animal to obtain a precision that is compatible with experimental studies. The methodology is compared with those used in earlier works involving estimates of neuron number in the rat hippocampus and a number of new stereological methods that have particular relevance to the quantitative study of the structure of the nervous system are briefly described in an appendix.

Animals↗
PubMed1991

Hypertension and components of vascular resistance.

1. In renal wrap hypertension in the rabbit and in essential hypertension in humans, non-autonomic components of resistance are the major factors contributing to elevated blood pressure. 2. The central nervous system plays an important role in moment to moment blood pressure control but is not responsible for maintenance of elevated pressure in essential hypertension. 3. Specific regions of the brain-stem maintain vascular tone through the effects of bulbospinal neurones which are organized both topographically and by chemical content. 4. Structural wall thickening in resistance vessels in hypertension is a manifestation of an abnormality of a growth controlling process. 5. Although several structural muscle growth factors have been identified, it is likely that only a few regulatory processes are critical. 6. Future studies in hypertension should examine associations between genetic markers of medial thickening and environmental influences.

Animals↗
PubMed1990

Unbiased stereological estimation of the number of neurons in the human hippocampus.

The total numbers of neurons in five subdivisions of human hippocampi were estimated using unbiased stereological principles and systematic sampling techniques. The method addresses the problems associated with the results and conclusions of previous quantitative studies, virtually all of which have been based on biased estimates of neuron densities. For each subdivision, the total number of neurons was calculated as the product of the estimate of the volume of the neuron-containing layers and the estimate of the numerical density of neurons in the layers. Each hippocampus was cut into 3-mm-thick slabs, transverse to the rostrocaudal axis. One 70-micron-thick section from each slab was used in the analysis. The volumes of the layers containing neurons in five major subdivisions of the hippocampus (granule cell layer, hilus, CA3-2, CA1, and subiculum) were estimated with point-counting techniques after delineation of the layers on each section. The numerical densities of neurons in each subdivision were estimated on the same sections with optical disectors. The sampling used in both estimates was performed systematically in all three dimensions. In an example of five hippocampi, the mean numbers of neurons (CV = SD/mean) in the different subdivisions were as follows: granule cells 15 X 10(6) (0.28), hilus 2.0 X 10(6) (0.16), CA3-2 2.7 X 10(6) (0.22), CA1 16 X 10(6) (0.32), subiculum 4.5 X 10(6) (0.19). The stereological measurements contributed approximately 25% of the observed variance. Among the five subjects there was a significant inverse relationship between age (which ranged from 47 to 85 years) and the total number of neurons in CA1 (which ranged from 24 to 11 X 10(6)). An optimized sampling scheme for studies of the number of neurons in the human hippocampus has been designed on the basis of an analysis of variance of the estimates at different levels of the sampling scheme. Counting neurons in the five subdivisions of the human hippocampus with the optimized sampling scheme takes less than 4 hours.

Aged↗
PubMed1990

The effect of low-level toluene exposure on the developing hippocampal region of the rat: histological evidence and volumetric findings.

With the intention of investigating possible morphological alterations effected by toluene in the developing CNS, rat pups were exposed to 100 ppm and 500 ppm of atmospheric toluene from postnatal day 1 until sacrifice at postnatal day 28, when the hippocampal region (area dentata, Ammon's horn, subiculum) was examined light microscopically and alterations in the volumes of the layers of the subdivisions were determined. The layers of Ammon's horn and the subiculum were not affected qualitatively or quantitatively by the 500 ppm exposure. Within the area dentata, the volume of the granule cell layer was 6% smaller in animals exposed to 100 ppm and 13% smaller in animals exposed to 500 ppm than they were in controls. The volumes of the hilus, which is a terminal field of granule cell axons, and the commissural-associational zone of the dentate molecular layer, which is the terminal field of the hilar projection to the granule cells, were smaller (12% and 19%) in animals exposed to 500 ppm than they were in controls. Argyrophilic cells were found in the granule cell layer of all animals exposed to 500 ppm. Pronounced granule cell degeneration was found in one animal exposed to 500 ppm. The granule cell layer of animals exposed to 100 ppm appeared qualitatively normal. The alterations reported here support the few earlier reports of morphological alterations in the CNS of adult laboratory animals. Effects of toluene similar to those described, that is alterations in specific neuron populations and their afferent and efferent terminal fields may complement changes in neurophysiology and behavior that have been observed in prenatally and perinatally exposed rodent pups. Causal relationships, however, remain to be elucidated.

Animals↗
PubMed1990

Communicating about communicating: when innate is not enough.

The cowbird is a brood parasite, providing no parental care to its offspring. The species has often been cited as a model of the usefullness of the construct of innate behavior, as an explanation of how young cowbirds develop species-typical behavior. Here we evaluate the adequacy of this perspective. We show that although it is difficult to explain ontogenetic beginnings without recourse to the concept of innate behaviors, ontogenetic outcomes are less easily accommodated. Constraints on the explanatory power of innateness as an ontogenetic concept are demonstrated with data from the development of singing in cowbirds and the development of babbling in human infants.

Animal Communication↗
PubMed1990

Cost-effective treatment of constipation in the elderly: a randomized double-blind comparison of sorbitol and lactulose.

PURPOSE: The purpose of this study was to evaluate the use of sorbitol as an inexpensive alternative to lactulose for treating constipation in the elderly. PATIENTS AND METHODS: Thirty men aged 65 to 86 with chronic constipation were studied in a randomized, double-blind, cross-over trial in which lactulose and 70% sorbitol (0 to 60 mL daily) were each given for 4 weeks preceded by a 2-week washout period. RESULTS: The average number of bowel movements per week was 6.71 with sorbitol and 7.02 with lactulose (95% confidence interval of the difference: -0.43 to 1.06), and the average number of days per week with bowel movements was 5.23 with sorbitol and 5.31 with lactulose (95% confidence interval of the difference: -0.32 to 0.48). Eleven patients stated a preference for sorbitol, 12 for lactulose, and seven had no preference. On a visual analogue scale measuring severity of constipation (0 to 100 mm), the average score for sorbitol was 35.6 mm versus 37.1 mm for lactulose (95% confidence interval of the difference: -6.4 to 9.3). The sorbitol and lactulose treatment periods were also similar in percent of bowel movements recorded as "normal," frequency and severity of symptoms such as bloating, cramping, and excessive flatulence, and overall health status as assessed by a previously validated five-category questionnaire. There were no significant differences between sorbitol and lactulose in any outcome measured except nausea, which was increased with lactulose (p less than 0.05). CONCLUSION: These results support the hypothesis that sorbitol and lactulose have no clinically significant differences in laxative effect. Sorbitol can be recommended as a cost-effective alternative to lactulose for the treatment of constipation in the elderly.

Aged↗
PubMed1990

Stereological studies of the hippocampus: a comparison of the hippocampal subdivisions of diverse species including hedgehogs, laboratory rodents, wild mice and men.

The volumes of the fascia dentata, hilus, regio inferior, regio superior and subiculum of 9 species that differ significantly in size and degree of forebrain evolution have been compared with the intent of identifying phylogenetic trends in the internal organization of the mammalian hippocampus. The study includes data from the hippocampi of a basal insectivore, 2 species of wild mice, 3 commonly used laboratory rodents and 3 species (including man) that resemble an ascending primate series. In addition to comparisons of the absolute and relative volumes, an allometric approach is used to identify "progressive" size differences not related to body size. Both regio superior and hilus become larger during evolution, while fascia dentata and regio inferior maintain a relationship to body size that is similar to that for the hippocampus in basal insectivores. The inter-species differences are discussed in terms of neuron number and size, for which data are presented from two species, and with reference to a neural model of the cognitive map theory for hippocampal function. Special emphasis is placed on the unique aspects of the human hippocampus. The data represents a quantitative morphological framework within which the observations from physiological, biochemical and behavioral studies in laboratory animals can be related to studies of the human hippocampus.

Animals↗
PubMed1990

Lack of effect of fish oil supplementation on blood pressure in treated hypertensives.

Fish and fish oils have been reported to reduce blood pressure in normotensives and untreated hypertensives. The present study examined the effect of dietary supplementation with fish oil on blood pressure in 20 treated hypertensives with controlled blood pressures who continued their usual antihypertensive drug treatment throughout. A double-blind, randomized crossover design was used, with two phases, each of 8 weeks' duration. In one phase, subjects took fifteen 1 g fish oil capsules (Lipitac; Reckitt and Colman Pharmaceuticals, Sydney, Australia) daily, and in the other, 15 capsules of identical appearance containing 1 g olive oil daily. There was no difference between the treatment phases for any blood pressure parameter, heart rate or body weight, but blood pressure was lower in both phases compared with pretreatment values. The fasting plasma triglyceride concentration was 30% lower in the fish oil phase (P less than 0.001), but there was no difference between the phases for plasma concentrations of total or high-density lipoprotein (HDL) cholesterol. We conclude that, in treated hypertensives with controlled blood pressures, any additional fall in blood pressure produced by dietary supplementation with fish oil is so small that the requirement for antihypertensive drug therapy is unlikely to be reduced.

Adult↗
PubMed1990

Diltiazem and atenolol in essential hypertension: additivity of effects on blood pressure and cardiac conduction with combination therapy.

In 15 patients with mild to moderate essential hypertension, the effects of diltiazem (120 mg twice daily) were compared with those of atenolol (50 mg once daily), the two drugs in combination, and placebo in a randomized double-blind cross-over study with treatment phases of 4 weeks duration. Blood pressure was reduced in the active treatment phases (supine blood pressure: diltiazem, 172/92 mmHg; atenolol, 172/92 mmHg; diltiazem plus atenolol, 164/88 mmHg; pooled estimate of s.e.m. by analysis of variance = 3/1) compared with placebo (180/101 mmHg). Factorial analysis confirmed fully additive antihypertensive effects of the drugs in combination. The time interval from the beginning of the P wave to the beginning of the QRS complex (P-R interval) was longer during combination therapy (0.184s) compared with either diltiazem (0.175s) or atenolol (0.174s) alone, or placebo (0.164s); s.e.m. by analysis of variance = 0.003. No clinically significant conduction disturbances occurred. Plasma atrial natriuretic peptide was elevated by atenolol but not diltiazem. Thus, in subjects with uncomplicated essential hypertension, diltiazem and atenolol had equal antihypertensive efficacy when used alone, and fully additive effects in combination, on both blood pressure and cardiac conduction.

Atenolol↗
PubMed1990

Automated non-invasive measurement of cardiac output by the carbon dioxide rebreathing method: comparisons with dye dilution and thermodilution.

The accuracy and reproducibility of indirect measurement of cardiac output at rest by the carbon dioxide rebreathing (indirect Fick) method with an automated respiratory analysis system (Gould 9000IV) were compared with simultaneous measurements made in duplicate by dye dilution and thermodilution in 25 patients having cardiac catheterisation studies. Measurements of cardiac output by the carbon dioxide rebreathing method were not significantly different from those obtained with dye dilution (mean difference -0.3 l/min, SD 0.76, 95% confidence interval -0.7 to 0.1). Thermodilution significantly over-estimated cardiac output by a mean of 2.2 l/min or 39% (SD 1.5, 95% confidence interval 1.6 to 2.8) compared with the carbon dioxide rebreathing method and significantly overestimated cardiac output by 1.9 l/min or 31% (SD 1.2, 95% confidence interval 1.2 to 2.5) compared with dye dilution. The reproducibility of measurements of cardiac output in individual patients was satisfactory with the dye dilution method but was poor with carbon dioxide rebreathing and thermodilution. Indirect measurement of resting cardiac output by the Gould 9000IV automated carbon dioxide rebreathing method is more accurate but the variability inherent with this method requires that multiple measurements be taken for each determination. Measurement of cardiac output by the thermodilution method by a commercially available cardiac output computer was not satisfactory because not only was there considerable variability between repeat measurements but the method also consistently overestimated cardiac output compared with the dye dilution method.

Adult↗
PubMed1990

Quantification of oral epithelial hyperplasia in rats after topical application of the carcinogen 4-nitroquinoline 1-oxide.

Hyperplasia of the palatal epithelium was quantified in two groups of rats exposed thrice weekly to the carcinogen 4NQO for 2 weeks and 2 months, respectively. The lengths and areas of the epithelial layers were measured with a computerized line-following device. In the group treated for 2 weeks the maximum area of the nuclear layer was nearly three times and the maximum length of the epithelial/connective tissue interface almost twice the normal at the end of the carcinogen application period. The maximum area of the cornified layer was three times and the maximum lengths of the epithelial surface and the keratin/nuclear layer interface almost one and a half times the normal 1 week after painting with 4NQO. Thereafter the lengths and areas decreased gradually in both experimental groups. The area of the cornified layer and the length of the epithelial/connective tissue interface in the group treated for 2 months were significantly larger than those in animals treated for 2 weeks. These variables may be two of several indicators of prognostic significance in the assessment of dose-related premalignant epithelial hyperplasia.

4-Nitroquinoline-1-oxide↗