N Lawson

Derby Hospitals NHS Foundation Trust, Derby, England, United Kingdom

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Publications (23)85.47 Total impact

  • Derek Pearson · Nigel Lawson ·
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    ABSTRACT: Clinical trials now run for many years. Sponsors need assurance that the instruments they use remain stable for that length of time and report consistent results. It is important, however, to clarify the difference between quality assurance (QA) and quality control (QC). During any process, there should be ongoing process control. This is usually an automatic feedback situation. QC is the ongoing sampling of the process being evaluated. This enables change in the process, but not normally immediately, unless sampling and analysis is rapid. QA is the evaluation of the QC process or audit. It is normally conducted periodically and is a sampling process of the QC process to ensure the described checks are being conducted, such as in a manufacturing line where, for example, washers are being made, the mean weight of the washers being produced can be evaluated. If the average weight of the washers varies beyond the predetermined limits, the mix can be adjusted to keep the washers within the basic limits. For every 100 washers made, one washer will be taken and carefully measured. If the washer is outside the predefined limits, the manufacturing process can be adjusted and, if necessary, stopped and restarted, to ensure the washers are made to specification (QC). Periodically, an audit will be made of the whole process to ensure everything was conducted to all the written specifications (QA).
    12/2006: pages 141-159;
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    Penny Blackwell · Ian M. Godber · Nigel Lawson ·
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    ABSTRACT: The routine clinical assessment of bone mineral density (BMD) is best undertaken by the use of dual-energy X-ray absorptiometry (DXA) and ultrasound scans. These techniques will establish BMD at a particular time. Using serial DXA measurements it is possible to measure a change in BMD over a set period of time. It is presumed that these measured changes in BMD are caused by alterations in bone turnover, but they are not direct measurements of bone turnover. Furthermore, DXA scans and ultrasound can only indicate that loss of BMD has occurred, a single measurement cannot indicate that bone loss is occurring, and might lead to a lowered BMD in the future. These radiological and ultrasound techniques have other limitations, not least inherent imprecision of the methods, which means that there have to be considerable changes in bone turnover before changes in BMD can be noticed. For example, the 1–2% imprecision of DXA measurement limits scanning to 6-monthly intervals, so that observed changes are certain to be owing to bone loss and not imprecision. The skilled nature of these techniques combined with the need for special equipment, and in the case of DXA exposure to ionizing radiation, has fueled the search for useful and reliable markers of bone turnover.
    12/2006: pages 247-269;
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    ABSTRACT: 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. 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. 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. 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). 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.
    Clinical & Experimental Allergy 09/2004; 34(8):1232-6. DOI:10.1111/j.1365-2222.2004.02032.x · 4.77 Impact Factor
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    O Sahota · M K Mundey · P San · I M Godber · N Lawson · D J Hosking ·
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    ABSTRACT: 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.
    Bone 07/2004; 35(1):312-9. DOI:10.1016/j.bone.2004.02.003 · 3.97 Impact Factor
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    ABSTRACT: Insulin-like growth factors (IGFs) are anabolic proteins that are essential regulators of cell division, differentiation and growth. We describe the longitudinal changes in IGF-I, IGF-II and the binding proteins IGFBP-1, -2 and -3 before and during normal pregnancy. Serum samples were taken before conception and then at 12, 24 and 36 weeks of gestation in 41 healthy women with uncomplicated pregnancies. We measured IGF-I using an automated chemiluminescent method, IGF-II and IGFBP-2 using in-house radioimmunoassays (RIAs), and IGFBP-1 and IGFBP-3 using commercial enzyme-linked immunosorbent assay (ELISA) and RIA kits, respectively. Because of the potential haemodilution effects during pregnancy, albumin was also measured in all samples. There was a significant fall in IGF-I during the first (36%) and second trimesters (21%) followed by an increase of 25% at 36 weeks. During pregnancy, the mean IGF-II concentrations fell by 12% at 12 weeks, 8% at 24 and 8% at 36 weeks compared with pre-conception values. When IGF-II results were adjusted for the haemodilution of pregnancy, its concentrations increased. During pregnancy, there was a rapid increase in mean IGFBP-1 levels by 17-fold (12 weeks), 24-fold (24 weeks) and 25-fold (36 weeks). IGFBP-2 concentrations fell after conception but started to increase towards term. This increase was more significant when adjusted for haemodilution. In contrast, IGFBP-3 concentrations increased significantly throughout pregnancy. Our data on the physiological changes of IGFs and their binding proteins add further evidence of the vital roles of these hormones throughout normal pregnancy.
    Annals of Clinical Biochemistry 06/2004; 41(Pt 3):220-6. DOI:10.1258/000456304323019596 · 2.34 Impact Factor
  • A Fogarty · E Broadfield · S Lewis · N Lawson · J Britton ·
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    ABSTRACT: 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.
    European Respiratory Journal 05/2004; 23(4):565-8. DOI:10.1183/09031936.04.00090404 · 7.64 Impact Factor
  • D Pearson · M Kaur · P San · N Lawson · P Baker · D Hosking ·
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    ABSTRACT: 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.
    Bone 03/2004; 34(3):570-8. DOI:10.1016/j.bone.2003.11.005 · 3.97 Impact Factor
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    ABSTRACT: Maternal calcium homeostasis adapts during pregnancy to provide for the needs of the growing fetal skeleton. Wide selections of bone turnover markers are currently available to assess the changes taking place; here, data are presented on two serum-based markers. The use of serum-based biochemical bone turnover markers during pregnancy was assessed in a cohort of 41 women recruited prior to conception. Serum N-terminal extension peptide of procollagen (P1NP) was used to monitor bone formation and serum beta-crosslaps (S-CTX) used to assess resorption. Blood samples were measured at five time points from a pre-conceptual baseline, through pregnancy, to the final sample, which was taken within 1 week of delivery. An initial decrease from the baseline in both P1NP and S-CTX was observed at 12 weeks; however, it is suggested that this may be due to the haemodilutional effect of pregnancy rather than a true change in bone turnover. Significant increases from the baseline of both analytes were observed by 36 weeks (P1NP, P = 0.013; S-CTX, P = 0.002), when the calcium demands of the fetus are greatest. This study illustrates the use of serum-based bone turnover markers to assess turnover during normal pregnancy, a time when ionizing radiation cannot be used to assess bone turnover.
    Annals of Clinical Biochemistry 10/2003; 40(Pt 5):508-13. DOI:10.1258/000456303322326416 · 2.34 Impact Factor
  • M Kaur · D Pearson · I Godber · N Lawson · P Baker · D Hosking ·
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    ABSTRACT: 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.
    Bone 04/2003; 32(4):449-54. DOI:10.1016/S8756-3282(03)00017-6 · 3.97 Impact Factor
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    ABSTRACT: Endothelium-derived nitric oxide is beneficial in experimental stroke. We assessed plasma NO levels in patients with acute stroke and their association with both severity and outcome. Plasma nitric oxide (NO), assessed as nitrate/nitrite (NOx), cyclic guanosine monophosphate (cGMP, second messenger to NO), L-arginine (substrate for NO) and L-citrulline (co-product with NO) levels were measured in 228 patients with acute ischemic stroke, 49 patients with acute hemorrhagic stroke, and 38 age and gender-matched normal volunteers. Stroke severity was assessed using the Glasgow Coma Scale, and the outcome was judged by discharge destination (home, institution, or dead). In our study, stroke patients had low levels of NOx (micromol/l): ischemic 49.9 (26.1); hemorrhage 41.7 (19.5); and control 64.0 (36.3) (P < .001); L-arginine (micromol/l): ischemic 85.1 (32.3); hemorrhage 69.9 (24.4); and control 104.0 (30.0) (P < .001); and L-citrulline (micromol/l): ischemic 30.5 (12.3); hemorrhage 26.7 (12.1); and control 39.4 (13.5) (P < .001). Cyclic GMP levels were elevated in stroke: ischemic 21.2 (16.1); hemorrhage 24.7 (17.5); and control 15.8 (9.2) (P = .024). Patients who died or became institutionalized had lower NOx, L-arginine, and L-citrulline levels, and higher cyclic GMP levels, than patients who were discharged home. NOx levels were not associated with feeding status in patients. Low levels of NOx are present in stroke and are associated with severity and outcome. Because endothelium-derived NO is beneficial in acute stroke, administering NO might be beneficial in acute stroke.
    Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 03/2003; 12(2):82-7. DOI:10.1053/jscd.2003.9 · 1.67 Impact Factor
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    ABSTRACT: Major differences in creatinine results between different laboratories and apparent inaccuracies when using commercial lyophilized standards were noted. In order to assess the variation and accuracy of the different methods we conducted a local audit. To establish the variation between methods, plasma creatinine was measured on 47 human plasma samples by nine different laboratories using four different methods (Roche, Ortho, Olympus, modified Olympus). To establish the accuracy of the different methods, plasma creatinine was also determined on 16 of the plasma samples by tandem mass spectrometry (MS). In addition, all the laboratories measured the creatinine concentration on a commercial authenticated sample. All four methods gave significantly different (P<0.0001) plasma creatinine results when compared with each other. Generally, creatinine results produced by the Ortho method were considerably higher than those of the other methods, especially at higher creatinine concentrations (differences across methods between the lowest and highest result for the same sample ranged between 8% and 33%). All four methods generally gave higher results than those determined by tandem MS for samples with creatinine concentrations of < 250 micromol/L. Above this concentration the Olympus and Roche methods produced creatinine results that were lower then the tandem MS results, whereas results from the Ortho method were higher. Major matrix problems were found when a commercial lyophilized standard was used for creatnine estimation. No method gave good agreement with the tandem MS results, and there were major differences in measured plasma creatinine concentrations (up to 30% difference) between the various methods. We suggest that efforts should be made to standardize plasma creatinine measurement across all laboratories to minimize these problems.
    Annals of Clinical Biochemistry 12/2002; 39(Pt 6):599-602. DOI:10.1258/000456302760413397 · 2.34 Impact Factor
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    ABSTRACT: Fragments of parathyroid hormone (PTH) have been identified (amino acids 7-84) which may interfere with commercially available 'intact molecule' PTH assays. Novel assays which employ an antibody directed to the first seven amino acids of the N-terminus of PTH are thought to be free from cross-reactivity with the 7-84 fragments, and therefore measure true 'whole molecule' PTH. Transplant recipients (as well as those in end-stage renal failure) have been reported to have elevated levels of 'intact' in comparison with 'whole molecule' PTH. PTH concentrations were assessed in serum samples obtained from female renal transplant recipients previously classified as either having hyperparathyroid (n = 14) or adynamic bone disease (n = 14) by transiliac crest bone biopsy. PTH was measured as 'whole molecule' (Scantibodies 'whole molecule' PTH) and 'intact' (DPC Immulite 2000 intact PTH and Scantibodies total PTH). Scantibodies 'whole molecule' PTH (all-subject mean 48.7 ng/L, +/- 53.0) were significantly lower than DPC intact (83.5 ng/L, +/- 88.1; P < or = 0.0001) and Scantibodies total PTH (80.5 ng/L, +/- 92.4; P < or = 0.0001). However, the differences between the 'whole molecule' and 'intact' measurements were similar across the two patient groups, and reflected the lower reference range employed by the 'whole molecule' assay. The 'whole molecule' PTH assay was unable to discriminate between the two patient populations and provided very little additional clinical information to that obtained from the intact PTH assays.
    Annals of Clinical Biochemistry 06/2002; 39(Pt 3):314-7. DOI:10.1258/0004563021902044 · 2.34 Impact Factor
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    I Crocker · N Lawson · J Fletcher ·
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    ABSTRACT: 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.
    Annals of the Rheumatic Diseases 05/2002; 61(4):307-10. DOI:10.1136/ard.61.4.307 · 10.38 Impact Factor
  • T Lang · P Prinsloo · A F Broughton · N Lawson · C B Marenah ·
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    ABSTRACT: 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. 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. 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.
    Annals of Clinical Biochemistry 01/2002; 39(Pt 1):66-7. DOI:10.1258/0004563021901586 · 2.34 Impact Factor
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    I P Crocker · N Lawson · P N Baker · J Fletcher ·
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    ABSTRACT: 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.
    QJM: monthly journal of the Association of Physicians 10/2001; 94(9):475-84. · 2.50 Impact Factor
  • O Sahota · I Fowler · P J Blackwell · N Lawson · SA Cawte · P San · T Masud · D J Hosking ·
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    ABSTRACT: 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.
    Osteoporosis International 11/2000; 11(11):959-66. DOI:10.1007/s001980070035 · 4.17 Impact Factor
  • A Broughton · C Marenah · N Lawson ·

    Annals of Clinical Biochemistry 06/2000; 37 ( Pt 3)(3):408-10. DOI:10.1258/0004563001899357 · 2.34 Impact Factor
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    I Crocker · N Lawson · I Daniels · P Baker · J Fletcher ·
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    ABSTRACT: 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.
    Clinical and Diagnostic Laboratory Immunology 08/1999; 6(4):587-93. DOI:10.1016/S1071-5576(97)86134-5 · 2.51 Impact Factor

  • Bone 05/1999; 24(5). DOI:10.1016/S8756-3282(99)00067-8 · 3.97 Impact Factor
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    ABSTRACT: 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.
    British Journal Of Nutrition 02/1998; 79(2):195-202. DOI:10.1079/BJN19980031 · 3.45 Impact Factor

Publication Stats

582 Citations
85.47 Total Impact Points


  • 2006
    • Derby Hospitals NHS Foundation Trust
      Derby, England, United Kingdom
  • 1995-2004
    • University of Nottingham
      • • School of Clinical Sciences
      • • School of Biomedical Sciences
      Nottigham, England, United Kingdom
  • 2002
    • Nottingham University Hospitals NHS Trust
      Nottigham, England, United Kingdom