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Biomedical subjects

N Lawson

Publications and source records attributed to N Lawson.

At least 19 recordsLinked to original sources
PubMed2004

Recovery of pregnancy mediated bone loss during lactation.

It is uncertain whether bone is routinely mobilised during pregnancy to provide calcium for the fetus and whether this is of a magnitude to cause osteoporosis. We have made sequential measurements of lumbar spine and hip bone mineral density (BMD) in 60 normal women before conception and then during the subsequent pregnancy out to one year after delivery. During pregnancy there was a significant fall in the BMD at the spine (1.53%), total hip (1.15%), and trochanter (3.90%) but not at the femoral neck. After delivery the women who breast-fed (n=34) showed a significant fall in BMD at all measurement sites (P<0.001) with the greatest change at the spine (4.7 +/- 3.1%) with 38% of women showing a change >5%. The women who bottle fed (n=10) increased or maintained BMD at all sites with the mixed feeders (n=16) showing an intermediate response. There was no consistent relationship between the change during pregnancy and lactation but 47% of the breast-feeders lost >5% at either the lumbar spine or trochanter. There was a good correlation between the change in BMD at these two sites (r=0.48, P<0.001). At 1 year after delivery all but 7 women had returned to within 5% of the preconceptual value at the spine and trochanter but the recovery at the total hip was less complete. Several women became transiently osteoporotic (T score below -2.5) at either spine or hip during reproduction of whom three started pregnancy with a normal BMD.

Adult↗
PubMed2004

The relationship between vitamin D and parathyroid hormone: calcium homeostasis, bone turnover, and bone mineral density in postmenopausal women with established osteoporosis.

It is evident from several studies that not all patients with hypovitaminosis D develop secondary hyperparathyroidism. What this means for bone biochemistry and bone mineral density (BMD) remains unclear. The aim of this study was to investigate the effects of hypovitaminosis D (defined as a 25OHD < or = 30 nmol/l) and patients with a blunted PTH response (defined arbitrarily as a PTH within the standard laboratory reference range in the presence of a 25OHD < or = 30 nmol/l) in comparison to patients with hypovitaminosis D and secondary hyperparathyroidism (defined arbitrarily as a PTH above the standard laboratory reference range in the presence of a 25OHD < or = 30 nmol/l) and vitamin D-replete subjects (25OHD > 30 nmol/l). Four hundred twenty-one postmenopausal women (mean age: 71.2 years) with established vertebral osteoporosis were evaluated by assessing mean serum calcium, 25OHD, 1,25(OH)2D, bone turnover markers, and BMD. The prevalence of hypovitaminosis D was 39%. Secondary hyperparathyroidism was found in only one-third of these patients who maintained calcium homeostasis at the expense of increased bone turnover relative to the vitamin D-replete subjects (bone ALP mean difference: 43.9 IU/l [95% CI: 24.8, 59.1], osteocalcin: 1.3 ng/ml [95% CI: 1.1, 2.5], free deoxypyridinoline mean difference: 2.6 nmol/nmol creatinine [95% CI: 2.5, 4.8]) and bone loss (total hip BMD mean difference: 0.11 g/cm2 [95% CI: 0.09, 0.12]). Patients with hypovitaminosis D and a blunted PTH response were characterized by a lower serum calcium (mean difference: 0.07 mmol/l [95% CI: 0.08, 0.2]), a reduction in bone turnover (bone ALP mean difference: 42.4 IU/l [95% CI: 27.8, 61.9], osteocalcin: 1.6 ng/ml [95% CI: 0.3, 3.1], free-deoxypyridinoline mean difference: 3.0 nmol/nmol creatinine [95% CI: 1.9, 5.9]), but protection in bone density (total hip BMD mean difference: 0.10 g/cm2, [95% CI: 0.08, 0.11]) as compared to those with hypovitaminosis D and secondary hyperparathyroidism. This study identifies a distinct group of patients with hypovitaminosis D and a blunted PTH response who show a disruption in calcium homeostasis but protected against PTH-mediated bone loss. This has clinical implications with respect to disease definition and may be important in deciding the optimal replacement therapy in patients with hypovitaminosis D but a blunted PTH response.

Aged↗
PubMed2004

A case-control study of dietary and erythrocyte membrane fatty acids in asthma.

BACKGROUND: Epidemiological evidence suggests that increased dietary omega-6 and reduced omega-3 fatty acid intake, may have contributed to the rising prevalence of asthma, but these hypotheses have not been tested in studies comparing both dietary intake and objective measures of polyunsaturated fatty acids. OBJECTIVE: To assess whether a higher intake of omega-6 or a lower intake of omega-3 fatty acids increases the risk of asthma, by measuring dietary fatty acid intake by a food frequency questionnaire (FFQ) and erythrocyte membrane fatty acids, as an objective biomarker of intake. METHODS: We have compared individual fatty acid intake estimated by FFQ and by mass spectrometry of fasting erythrocyte cell membranes in 89 cases of asthma and 89 community-matched controls. RESULTS: The odds of asthma were increased in relation to intake of the omega-3 fatty acids eicosapentaenoic acid (odds ratio (OR) for difference between the 25th and 75th centiles of intake= 1.89, 95% CI 1.15-3.11) and docosahexaenoic acid (OR = 2.11, 95% CI 1.19-3.74). There was no evidence of any difference in erythrocyte membrane levels of omega-3 fatty acids, while the odds of asthma were reduced in relation to linoleic acid (omega-6) membrane levels (OR = 0.45, 95% CI 0.21-0.95). CONCLUSION: These findings suggest that dietary omega-3 fatty acids do not play a major role in protecting against asthma, and that higher levels of erythrocyte membrane linoleic acid are associated with a lower risk of asthma.

Adult↗
PubMed2004

Amino acids and asthma: a case-control study.

Amino acids contribute to various anti-oxidant and immunological activities relevant to asthma pathogenesis, raising the possibility that differences in amino acids may be involved in asthma aetiology. The authors hypothesised that cystine reduces the risk of asthma via glutathione metabolism. Methionine, glutamine, glutamic acid and glycine may have potential protective effects, whilst arginine, phenylalanine and tryptophan may have adverse effects in asthma. Fasting plasma levels of amino acids were compared in a case-control study. A total of 89 adults, aged 18-65 yrs, with asthma controlled by inhaled corticosteroids, were recruited from a volunteer database and local primary care registers, and compared with 89 controls individually matched for age, sex and primary care centre. Contrary to the primary hypothesis, cases had higher fasting plasma cystine levels than controls, and there was no difference between cases and controls in any of the other amino acids tested, with the exception of plasma glycine, which was associated with a strongly reduced risk of asthma (odds ratio for the highest tertile compared to lowest 0.30 (95% confidence interval (0.11-0.82)). This study negates the hypothesis that higher fasting plasma cystine levels have a protective effect on the risk of asthma, although the inverse correlation with plasma glycine deserves further investigation.

Adolescent↗
PubMed2003

Longitudinal changes in bone mineral density during normal pregnancy.

Pregnancy is a common physiological event that could affect peak bone mass and the risk of developing osteoporosis later in life. There have been few longitudinal studies over a complete reproductive cycle of any size to show whether bone mineral density (BMD) changes. We have measured BMD by dual-energy X-ray absorptiometry in 46 normal women before conception and then again immediately after delivery and compared them with 30 control women who failed to conceive. Fifteen women were osteopenic in preconceptual BMD, but there was no difference between those who did or did not become pregnant. During pregnancy there was a small and statistically nonsignificant decline in BMD at all sites. The decrease at the trochanteric region was 4.2%, while losses at other sites were about 1%. The decline at the trochanter exceeded the least significant change between two measurements (5.04%) in 17 women (40.5%) with significant changes within individuals being much less common at the other measurement sites. The nonpregnant controls showed small increases in BMD of 0.3%-1.9% but no woman lost more than the least significant change. At the trochanter there was a significant difference (P = 0.013) between those who did and did not become pregnant. There was a good correlation between changes in BMD at all sites and no significant difference in the slope of these correlations between the pregnant and control groups. Correlations with lumbar spine were total hip, r = 0.46, P = 0.0001; femoral neck, r = 0.49, P = 0.0005; and trochanter, r = 0.66, P < 0.0001.

Absorptiometry, Photon↗
PubMed2002

Effect of pregnancy and obstructive jaundice on inflammatory diseases: the work of P S Hench revisited.

Hench considered that cortisone improved inflammatory joint symptoms during pregnancy and obstructive jaundice. However, the improved symptoms are probably due to changes in the proportions of fatty acids in plasma and inflammatory cell phospholipids. These changes decrease the superoxide anions and eicosanoids produced and also reduce tumour necrosis factor alpha production.

Adrenal Cortex Hormones↗
PubMed2002

Effect of low protein concentration on serum sodium measurement: pseudohypernatraemia and pseudonormonatraemia!

BACKGROUND: The effect of high concentrations of protein or lipid on the measurement of plasma sodium by indirect ion selective electrode (ISE) causing pseudohyponatraemia and pseudonormonatraemia is well described. The effect of a low total protein concentration, however, has not been described. METHODS: In order to examine this, over a 2-week period the total protein concentration was measured on all samples received for urea and electrolyte measurement. All samples with a low (<50 g/L) or a high (> 80 g/L) total protein concentration had sodium measured by both direct and indirect ISE. RESULTS: There were approximately equal numbers of samples with a protein concentration less than 50 g/L (1.3%) as samples with a protein concentration greater than 80 g/L (1.3%). The frequency of erroneous sodium results owing to the use of an indirect ISE was less in hypoproteinaemic (2%) than in hyperproteinaemic (20%) samples.

Blood Proteins↗
PubMed2001

The anti-inflammatory effects of circulating fatty acids in obstructive jaundice: similarities with pregnancy-induced immunosuppression.

Rheumatoid arthritis (RA) is ameliorated during both obstructive jaundice and pregnancy. Previous studies of polymorphonuclear leukocyte (PMN) function during pregnancy have shown reductions in the stimulated release of arachidonic acid (AA) and leukotriene B4 (LTB4), and lower NADPH oxidase activity. These changes may account for the amelioration of RA. The cause of this reduction in PMN function appears to be a progressive change in circulating fatty acids (FA), with a reduction in polyunsaturated FA, predominantly AA. The NADPH oxidase responsible for the respiratory burst has a direct requirement for polyunsaturated FA, particularly AA. We investigated whether the same changes in PMN function and FA, occur during obstructive jaundice. Patients with biliary obstructions were investigated before and after surgical correction (n=14). Obstructive jaundice caused significant changes in the proportions of serum and cellular FA. There was a striking reduction in polyunsaturated FA, particularly AA (48% in serum, p<0.001; 42% in PMNs, p<0.001) and an increase in mono-unsaturated oleic acid (24% in serum, p<0.001; 15% in PMNs, p<0.005). Similar changes occurred in mononuclear cell FA. Jaundice also caused a significant reduction in PMN function. Respiratory burst activity was reduced by between 32% and 38% in response to physiological and non-physiological stimuli, and there were similar significant reductions in the release of AA and LTB4. These changes in stimulated PMN function were evident whether or not the cells were first primed with tumour necrosis factor alpha (TNFalpha). Incubation of PMNs from healthy donors in pooled serum from patients with obstructive jaundice caused a reduction of 32% in cellular AA and 38% in NADPH oxidase activity. These findings support the idea that circulating FA can regulate PMN inflammatory responsiveness. The FA-induced attenuation in PMN activity in both jaundice and pregnancy may explain their ameliorating effects upon RA.

Adult↗
PubMed2000

A comparison of continuous alendronate, cyclical alendronate and cyclical etidronate with calcitriol in the treatment of postmenopausal vertebral osteoporosis: a randomized controlled trial.

A number of drugs are now available for the treatment of established osteoporosis and have been shown to significantly increase bone mineral density (BMD). There are, however, few comparative treatment studies and, furthermore, adverse events remain a problem with some of the newer agents, particularly in the elderly, in everyday clinical practice. We report a 12 month, open labeled, randomized controlled, prospective treatment study in 140 postmenopausal women with established vertebral osteoporosis, comparing the effect of continuous alendronate, cyclical alendronate and cyclical etidronate with calcitriol in terms of gain in BMD, reduction in bone turnover markers and adverse event profile. The mean percentage increases in BMD at 12 months, at the spine and hip respectively, were: continuous alendronate 5.7%, 2.6%; cyclical alendronate 4.1%, 1.6%; cyclical etidronate 4.9%, 2.0% (p<0.0 1) and calcitriol 2.0%, 0.4% (NS). In comparison with calcitriol, the mean changes in BMD at the spine and hip respectively were greater in the other groups; continuous alendronate: 3.7% (95% CI 1.4 to 8.3), 2.2% (95% CI 0.7 to 4.0); cyclical alendronate: 2.1% (95% CI 1.2 to 6.4), 1.2% (95% CI -0.3 to 3.0); cyclical etidronate: 2.9% (95% CI 1.9 to 6.5), 1.6% (95% CI 0.9 to 3.1)). The reduction in bone turnover markers was between 26% and 32% in the alendronate and etidronate groups (p<0.01), with a trend toward greater reduction in the continuous alendronate group. Eight patients discontinued the study: 6 in the continuous alendronate group, 1 in the cyclical alendronate group and 1 in the calcitriol group. Two patients in the cyclical etidronate group were unable to tolerate the Cacit component, but continued on substituting Cacit with Calcichew. In summary, 12 months of treatment with continuous alendronate, cyclical alendronate and cyclical etidronate are effective in terms of the gain in BMD at the anteroposterior spine and total hip in a comparable treatment population. These treatments are more effective than calcitriol and were generally well tolerated. Continuous alendronate showed a trend toward a larger gain in BMD and greater suppression of bone turnover markers than the other treatment groups, but had a higher incidence of adverse events, particularly within the older subgroup. Cyclical alendronate offers a lower adverse event profile and appears to be effective in comparison with continuous treatment, and may possibly be an alternative in the elderly. However, further studies are necessary, but more importantly with fracture end-points.

Administration, Oral↗
PubMed2000

Measurement of urinary free cortisol using the Acs:180 serum cortisol chemiluminescent immunoassay.

Measurement of urinary free cortisol using the Bayer Automated Chemiluminescent System (ACS:180 PLUS) was evaluated and compared with an in-house extraction radioimmunoassay (RIA). Inter-assay coefficients of variation were acceptable, being respectively 5.3%, 4.8% and 3.8% at 141, 406 and 942 nmol/L (n=20) for the ACS direct assay and 19.4% and 12.1% at 27 and 116 nmol/L with dichloromethane extraction (n=10). Using tritiated cortisol, mean extraction efficiency for the ACS extraction protocol was 89% compared with 104% for the RIA method (n=6, P<0.001) and using urine spiked with ACS serum calibrator, extraction efficiency was only 76% (standard deviation 8.8%, n=49) on the ACS. Urine spiked with cortisol dissolved in ethanol also gave significantly lower recoveries on the ACS for both direct and extraction methods compared with the RIA. Regression analysis of results from a mixture of control serum samples and samples from patients (n=93) showed good correlations between the direct and extraction ACS methods and the RIA extraction assay. The median concentration in 23 normal subjects and 95% reference intervals (nmol/24 h) were: ACS direct, 237 (135-505); ACS extraction, 91 (33-239); and RIA extraction, 146 (80-334). 5Beta-dihydrocortisol was the only major interferent in all assays. The ACS extraction assay showed acceptable performance and correlated well with the extraction RIA, although there was evidence of matrix-dependent effects causing low recovery.

Case-Control Studies↗
PubMed1999

Significance of fatty acids in pregnancy-induced immunosuppression.

Pregnancy can exert suppressive effects on chronic inflammatory conditions. We have previously demonstrated a depression in polymorphonuclear leukocyte (PMN) respiratory burst during pregnancy which could explain this amelioration. To elucidate the biochemical mechanism, we have examined PMN phospholipase A2 (PLA2) activity and its relationship to cellular and circulating fatty acids in pregnant women (30 to 34 weeks) and nonpregnant controls. PMN PLA2 activity was determined by arachidonic acid (AA) and leukotriene B4 (LTB4) release, respiratory burst activity was determined by lucigenin-enhanced chemiluminescence, and total serum and PMN fatty acid levels were determined by gas-liquid chromatography. AA release was significantly reduced for pregnancy PMNs in response to N-formyl-met-leu-phe (fMLP) under unprimed and tumor necrosis factor alpha (TNF-alpha)- or interleukin 8-primed conditions. Similarly, LTB4 liberation was significantly reduced in response to fMLP and phorbol myristate acetate in unprimed and TNF-alpha-primed pregnancy PMNs. All major fatty acid classes were altered in the pregnant state. Of these differences in PMNs, oleic acid and alpha-linolenic acid showed a significant increase (13 and 26%, respectively) and stearic acid and AA showed a significant decrease (8 and 30%, respectively). The stearic acid, oleic acid, and AA compositions of all cells analyzed correlated with their corresponding changes in serum fatty acid levels. Crossover serum incubations modified both fatty acid profiles and the PMN respiratory burst accordingly, while individual fatty acid incorporation studies highlighted the importance of polyunsaturated fatty acids for NADPH oxidase efficiency. These findings indicate that the attenuation of PMN function in pregnancy may originate from a reduction in the available pool of cellular fatty acids. Furthermore, this reduction arises as a direct result of a pregnancy-induced shift in circulating fatty acids from polyunsaturated to monounsaturated forms.

Adolescent↗
PubMed1998

The effect of different dietary fatty acids on lipoprotein metabolism: concentration-dependent effects of diets enriched in oleic, myristic, palmitic and stearic acids.

While it is well established that the fatty acid composition of dietary fat is important in determining plasma lipoprotein cholesterol concentrations, the effects of changing the absolute quantities of the individual fatty acids are less clear. In the present study Golden Syrian hamsters were fed on isoenergetic, low cholesterol (0.05 g/kg) diets containing 100, 150 or 200 g added fat/kg. This consisted of triolein (TO) alone, or equal proportions of TO and either trimyristin (TM), tripalmitin (TP) or tristearin (TS). Each trial also included a control group fed on a diet containing 50 g TO/kg. As the mass of TO in the diet increased, plasma VLDL-cholesterol concentrations rose. The TM-rich diets produced a concentration-dependent increase in total plasma cholesterol which was a result of significant increases in both VLDL and HDL levels. The TP-rich diets increased plasma LDL- and HDL-cholesterol levels in a concentration-dependent manner. TS-containing diets did not increase the cholesterol content of any of the major lipoprotein fractions. Hepatic LDL-receptor mRNA concentrations were significantly decreased in animals fed on TP, while apolipoprotein B mRNA concentrations were significantly increased. Thus, on a low-cholesterol diet, increasing the absolute amount of dietary palmitic acid increases LDL-cholesterol more than either myristic or stearic acid. These effects on lipoprotein metabolism may be exerted through specific modulation of the expression of the LDL receptor and apolipoprotein B genes.

Animals↗
PubMed1997

Pituitary dysfunction in recently post-menopausal women. Nottingham EPIC Study Group.

OBJECTIVE: Some recently post-menopausal women have lower than expected FSH concentrations, raising the possibility of subclinical hypothalamo-pituitary impairment. We have therefore performed pituitary stimulation tests in a group of recently post-menopausal women recruited to a bone loss prevention study. DESIGN: Prospective study of health volunteers. SETTING: Outpatient, teaching hospital in Nottingham UK. SUBJECTS: Forty-seven women selected from a cohort of 428 healthy volunteers to an osteoporosis prevention study all within 10 years of the menopause. MAIN OUTCOME MEASURES: Response of the pituitary to formal stimulation tests and its relationship to bone mineral density. RESULTS: A significantly attenuated response to pituitary stimulation was found in a group of otherwise healthy women with an FSH considered to be inappropriately low for the level of circulating oestradiol. The impaired responses were significant not only for FSH as expected but also to LH and prolactin at 1 hour after injection of GnRH and TRH (area under the curve, FSH P = 0.01, LH P = 0.001, prolactin P < 0.0001). TSH secretion was not significantly impaired. Baseline cortisol, growth hormone and thyroxine (T4) were normal in both control and test subjects. The test group was both heavier and taller, with a higher lean body mass, a higher body mass index and a greater total body fat than the controls. Bone mineral density showed no significant differences between the groups. Test subjects also had a higher free oestradiol index (P < 0.001) which correlated strongly (r = 0.534, P = 0.00026) with baseline FSH levels and possibly reflects a greater tissue exposure to biologically active hormone. Oestrone concentrations were, however, no different between the groups. CONCLUSIONS: Serum FSH concentrations are not invariably elevated in recently post-menopausal women and use of FSH as a determinant for postmenopausal status in clinical trials should be used with caution. Notwithstanding their higher free oestradiol index, women found to have an abnormally low basal FSH had evidence of poor prolactin, FSH and LH but not TSH responses to pituitary stimulation. This may represent either a degree of subclinical pituitary failure of a variant of normal. The low levels of gonadotrophin activity did not affect bone mineral density.

Bone Density↗
PubMed1997

Control of late neutrophil-specific gene expression: insights into regulation of myeloid differentiation.

During myeloid differentiation, the pluripotent hematopoietic stem cell passes through several well-defined morphologic stages within the bone marrow. These changes include progressive nuclear segmentation and the acquisition of stage-specific granules. Primary granules appear at the myeloblast stage, and are found in both neutrophils and monocytes. At the myelocyte stage, neutrophil precursors acquire specific granules, a marker of commitment to terminal neutrophil differentiation. This complex developmental pathway is just beginning to be elucidated. Current evidence suggests that myeloid differentiation is regulated primarily by transcriptional regulatory proteins, and that dysfunction of those regulators is involved in most disorders of neutrophil maturation. Furthermore, there is evidence that study of late gene expression may provide insights into more proximal events in granulocytic maturation. In this review, we provide a brief overview of myeloid differentiation with emphasis on the culture systems available for the study of granulopoiesis and the insights they provide into the regulation of late neutrophil-specific gene expression. We discuss the relevance of these observations to our understanding of the pathogenesis of defects in neutrophil differentiation.

Animals↗