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M Lawrence

Publications and source records attributed to M Lawrence.

At least 19 recordsLinked to original sources
PubMed2006

The global atmospheric environment for the next generation.

Air quality, ecosystem exposure to nitrogen deposition, and climate change are intimately coupled problems: we assess changes in the global atmospheric environment between 2000 and 2030 using 26 state-of-the-art global atmospheric chemistry models and three different emissions scenarios. The first (CLE) scenario reflects implementation of current air quality legislation around the world, while the second (MFR) represents a more optimistic case in which all currently feasible technologies are applied to achieve maximum emission reductions. We contrast these scenarios with the more pessimistic IPCC SRES A2 scenario. Ensemble simulations for the year 2000 are consistent among models and show a reasonable agreement with surface ozone, wet deposition, and NO2 satellite observations. Large parts of the world are currently exposed to high ozone concentrations and high deposition of nitrogen to ecosystems. By 2030, global surface ozone is calculated to increase globally by 1.5 +/- 1.2 ppb (CLE) and 4.3 +/- 2.2 ppb (A2), using the ensemble mean model results and associated +/-1 sigma standard deviations. Only the progressive MFR scenario will reduce ozone, by -2.3 +/- 1.1 ppb. Climate change is expected to modify surface ozone by -0.8 +/- 0.6 ppb, with larger decreases over sea than over land. Radiative forcing by ozone increases by 63 +/- 15 and 155 +/- 37 mW m(-2) for CLE and A2, respectively, and decreases by -45 +/- 15 mW m(-2) for MFR. We compute that at present 10.1% of the global natural terrestrial ecosystems are exposed to nitrogen deposition above a critical load of 1 g N m(-2) yr(-1). These percentages increase by 2030 to 15.8% (CLE), 10.5% (MFR), and 25% (A2). This study shows the importance of enforcing current worldwide air quality legislation and the major benefits of going further. Nonattainment of these air quality policy objectives, such as expressed by the SRES-A2 scenario, would further degrade the global atmospheric environment.

Air Pollutants↗
PubMed2001

Mometasone furoate: efficacy and safety in moderate asthma compared with beclomethasone dipropionate.

BACKGROUND: Mometasone furoate (MF) is a new inhaled glucocorticoid administered by dry powder inhaler (DPI). OBJECTIVE: MF-DPI was evaluated for safety and efficacy and compared with placebo DPI and beclomethasone dipropionate (BDP) administered by metered dose inhaler (MDI) in the treatment of patients with moderate persistent asthma. METHODS: Eligible patients (n = 227), 13 to 75 years of age, maintained on inhaled glucocorticoids before entering the trial, were randomized to receive: MF-DPI, 100 microg, twice daily, MF-DPI, 200 microg, twice daily, BDP MDI, 168 microg, twice daily, or placebo in a 12-week, multicenter, double-blind study. RESULTS: At endpoint, FEV1 (primary efficacy variable) significantly improved for all three active treatments compared with placebo (P < .01, all comparisons). The response to MF-DPI, 200 microg, twice daily treatment was approximately twice as large as the response to MF-DPI, 100 microg, twice daily or BDP MDI treatment, although the differences between these groups did not reach statistical significance. Secondary efficacy variables including PEFR, asthma symptoms, nocturnal awakenings, and albuterol use showed similar trends. The MF-DPI, 100 microg, twice daily and BDP MDI, 168 microg, twice daily treatment groups produced comparable results for all efficacy variables. CONCLUSIONS: MF-DPI, 100 microg and 200 microg, twice daily were well-tolerated and significantly improved lung function and symptom control in the treatment of patients with moderate persistent asthma. In this study, MF-DPI, 200 microg, twice daily seemed to be the most effective dosage.

Administration, Inhalation↗
PubMed2001

Neighbourhood renewal and health: evidence from a local case study.

This article presents findings from a before-and-after study of the effects of neighbourhood renewal on residents' health. Survey data were analysed using multivariate logistic regression. Before the renewal programme, damp and draughts had significant independent effects on respiratory health problems. Draughts and perceived community safety were associated with mental health problems. Children's mental health was associated with parental mental health. Following the renewal work, improvements occurred in both adults' and children's mental health, and smoking declined sharply. Respiratory health did not improve and there was no change in use of health services. Neighbourhood renewal in deprived areas can have an important role in improving community health.

Adolescent↗
PubMed2001

Loving them to death: the anorexic and her objects.

The author suggests that eating disorders function to reinforce phantasies of control of the internal parents, a feature of Klein's view of the manic defence. Using this hypothesis, she attempts to differentiate between anorexia and bulimia. It is argued that in anorexia objects are felt to be permanently in thrall, suspended or frozen, whereas in bulimia they are attacked in a frenzied and intermittent way. Using case material from three seriously ill patients, the author draws attention to some important differences between them. Two of the patients were treated in psychoanalysis, while the third was seen for an extended consultation and once-weekly treatment thereafter. It is suggested that the nature and degree of the murderous attack on the internal couple may determine the severity of the illness as well as the patient's capacity to benefit from treatment. The conclusions drawn are discussed in relation to some contemporary views on eating disorders as well as writings on the difficulties of working through the Oedipus complex more generally. The author suggests that eating disorders may represent a special case of oedipal illusions.

Adult↗
PubMed2000

Cardiovascular malformations and other cardiovascular abnormalities in neurofibromatosis 1.

Although it is well recognized that a peripheral vasculopathy may occur in patients with neurofibromatosis 1 (NF1), it is unclear whether cardiovascular abnormalities are more common. We reviewed the frequency of cardiovascular abnormalities, in particular, cardiovascular malformations (CVMs), among 2322 patients with definite NF1 in the National Neurofibromatosis Foundation International Database from 1991-98. Cardiovascular malformations were reported in 54/2322 (2.3%) of the NF1 patients, only 4 of whom had Watson syndrome or NF1-Noonan syndrome. There was a predominance of Class II "flow" defects [Clark, 1995: Moss and Adams' Heart Disease in Infants, Children, and Adolescents Including the Fetus and Young Adult. p 60-70] (43/54, 80%) among the NF1 patients with CVMs. Pulmonic stenosis, that was present in 25 NF1 patients, and aortic coarctation, that occurred in 5, constitute much larger proportions of all CVMs than expected. Of interest was the paucity of Class I conotruncal defects (2 patients with tetralogy of Fallot), and the absence of atrioventricular canal, anomalous pulmonary venous return, complex single ventricle and laterality defects. Besides the 54 patients with CVMs, there were 27 patients with other cardiac abnormalities (16 with murmur, 5 with mitral valve prolapse, 1 with intracardiac tumor, and 5 with electrocardiogram abnormalities). No patient in this study had hypertrophic cardiomyopathy. There were 16 patients who had a peripheral vascular abnormality without an intracardiac CVM, plus an additional 4 patients among those with a CVM who also had a peripheral vascular abnormality.

Aortic Coarctation↗
PubMed2000

Sparing of neuronal function postseizure with gene therapy.

Numerous studies have demonstrated that gene therapy interventions can protect neurons from death after neurological insults. In nearly all such studies, however, "protection" consists of reduced neurotoxicity, with no demonstrated preservation of neuronal function. We used a herpes simplex virus-1 system to overexpress either the Glut-1 glucose transporter (GT) (to buffer energetics), or the apoptosis inhibitor Bcl-2. Both decreased hippocampal neuron loss to similar extents during excitotoxic insults in vitro and in vivo. However, the mediating mechanisms and consequences of the two interventions differed. GT overexpression attenuated early, energy-dependent facets of cell death, blocking oxygen radical accumulation. Bcl-2 expression, in contrast, blocked components of death downstream from the energetic and oxidative facets. Most importantly, GT- but not Bcl-2-mediated protection preserved hippocampal function as assessed spatial maze performance. Thus, gene therapeutic sparing of neurons from insult-induced death does not necessarily translate into sparing of function.

Animals↗
PubMed2000

Systematic review of the epidemiological evidence on Helicobacter pylori infection and nonulcer or uninvestigated dyspepsia.

BACKGROUND: Previous studies have yielded conflicting results and substantial uncertainty about any independent association of Helicobacter pylori infection with dyspepsia, and about any benefits of antibiotic treatments for nonulcer or uninvestigated dyspepsia. OBJECTIVES: To perform a systematic review of the literature to determine whether chronic infection with H pylori is relevant to nonulcer or uninvestigated dyspepsia. METHODS: Observational studies of associations between H pylori and dyspepsia published before April 1999 and randomized trials of the effects of H pylori eradication on dyspepsia published before January 2000 were identified by computer-assisted literature searches of relevant journals, reference lists, and discussions with authors. Relevant data were abstracted from the published reports by 2 investigators according to a fixed protocol. RESULTS: Thirty relevant observational studies were identified involving approximately 3392 patients with nonulcer dyspepsia, and 11 separate observational studies were identified, involving 6426 patients with uninvestigated dyspepsia. Reports of strong associations in small observational studies without appropriate adjustment for potential confounding factors were not generally confirmed by larger and better-designed studies. No studies have been reported, however, that can reliably confirm or exclude the existence of any weak associations. Twenty-two randomized trials of treatments against H pylori were found involving a total of 2340 patients with nonulcer dyspepsia, almost all with positive H pylori test results. Only a few of these trials involved effective antibacterial regimens with prolonged follow-up, and even these studies were too small to assess the possibility of moderate benefits. CONCLUSION: The available evidence indicates that there is no strong association between H pylori and dyspepsia, but there is insufficient evidence to confirm or refute the existence of a modest association.

Chronic Disease↗
PubMed2000

Once-daily mometasone furoate dry powder inhaler in the treatment of patients with persistent asthma.

BACKGROUND: Although inhaled glucocorticoids are recommended for all stages of persistent asthma, compliance with long-term therapy is often poor, leading to significant morbidity and mortality. A simplified, once-daily dosing regimen may foster improved compliance. OBJECTIVE: To compare the efficacy and safety of once-daily (AM) administration of mometasone furoate dry powder inhaler (MF DPI) 200 microg and 400 microg with placebo in patients with asthma previously maintained only on short-acting inhaled beta-adrenergic receptor agonists. METHODS: This was a 12-week, double-blind, placebo-controlled, parallel group study. The mean change from baseline to endpoint (last treatment visit) for FEV1 was the primary efficacy variable. RESULTS: At endpoint, both doses of MF DPI were significantly more effective than placebo (P < or = .05) in improving FEV1. Based on morning peak expiratory flow rate, once-daily MF DPI 400 microg was more effective than placebo (P < or = .001) at endpoint. Both active treatments also demonstrated improvement at endpoint in asthma symptom scores, physician-evaluated response to therapy and use of rescue medication. Although both MF DPI dosages were efficacious, MF DPI 400 microg provided additional improvement in some measures of pulmonary function (eg, morning PEFR) when these agents were administered once daily in the morning. Both doses of MF DPI were well tolerated and treatment-related adverse events occurred at a similar incidence among the three treatment groups. CONCLUSIONS: The results of this study indicate that once-daily (AM) MF DPI provides a convenient and effective treatment option for patients with mild or moderate persistent asthma.

Adolescent↗
PubMed2000

Comparison of powder and aerosol formulations of salmeterol in the treatment of asthma.

BACKGROUND: The efficacy and safety of the aerosol metered-dose inhaler (MDI) formulation of salmeterol for asthma symptoms have been established. Recently, salmeterol has been introduced as a micronized powder formulation administered via a breath-activated multidose powder inhaler (Diskus). OBJECTIVE: A multicenter, randomized, double-blind, double-dummy, parallel-group, placebo-controlled study involving 498 adolescents and adults with mild-to-moderate asthma was conducted to compare the efficacy and safety of salmeterol powder 50 microg twice daily via Diskus, salmeterol aerosol 42 microg twice daily via MDI, and placebo. METHODS: Patients were randomized to one of the three treatment groups for 12 weeks. Efficacy was assessed by serial measurements of forced expiratory volume in one second (FEV1) over 12 hours, daily peak expiratory flow (PEF), self-rated asthma symptom scores, nighttime awakenings, and supplemental albuterol use. Safety of each treatment was evaluated by monitoring vital signs, electrocardiograms, Holter monitoring, and occurrence of adverse events. RESULTS: As compared with placebo, both salmeterol powder and aerosol produced significant improvement in FEV1 and PEF and decreased nighttime awakenings and supplemental albuterol use. There were no significant differences in the efficacy of the two salmeterol formulations. The magnitude of improvement in pulmonary function was undiminished over the 12-week study. Both formulations of salmeterol were well tolerated, with safety profiles not significantly different from placebo. CONCLUSION: Results of this study indicate that salmeterol, administered either as a powder 50 microg twice daily via Diskus or as an aerosol 42 microg twice daily via MDI, produces clinically significant and comparable improvement in pulmonary function and is well tolerated in patients with mild-to-moderate persistent asthma.

Adolescent↗
PubMed2000

Immediate-release oxybutynin versus tolterodine in detrusor overactivity: a population analysis.

We evaluated adherence to treatment with immediate-release (IR) oxybutynin (515 patients) and tolterodine (505 patients) for detrusor overactivity through retrospective analysis of a pharmacy claims database. Outcomes included percentage of patients continuing therapy for 6 months, medication possession ratios, and time to discontinuation of therapy. The proportion of patients continuing therapy for 6 months was statistically superior for tolterodine (32%) compared with IR oxybutynin (22%, p<0.001). Medication possession ratios were also superior for patients in the tolterodine group (medians 0.83 and 0.64, ranges 0.11-1.15 and 0.07-1.13, respectively, p<0.001). Oxybutynin was discontinued significantly earlier (mean 45 days) than tolterodine (mean 59 days, p<0.001) and was switched to another therapy more commonly than tolterodine (19% and 14%, respectively). Tolterodine was favored over oxybutynin for several measurements of patient adherence. However, less than one-third of patients continued therapy with either agent for 6 months. The clinical relevance of these differences is unknown.

Adolescent↗
PubMed1999

Pneumocystis carinii pneumonia in HIV-infected patients: effect of steroid therapy on surfactant level.

Previous studies have suggested alterations in pulmonary surfactant lipid in the setting of Pneumocystis carinii pneumonia in HIV-infected patients. Because pulmonary surfactant lipid is composed of a variety of lipid products and because other phospholipids might be present in bronchoalveolar lavage (BAL) lipid determinations, a single molecular species of phospholipid which comprises a substantial portion of the surfactant lipid fraction, dipalmitoyl phosphatidylcholine (DPPC), was measured by capillary column gas chromatography in BAL samples taken at the time of the diagnosis of P. carinii pneumonia, and 10 days after treatment for P. carinii pneumonia. DPPC was measured at day 0 and day 10 in seven patients who had been randomized to receive methylprednisolone adjuvant therapy for P. carinii pneumonia and in six patients who had been randomized to not receive methylprednisolone therapy. The level of DPPC in BAL from all patients at day 0 was 0.49 +/- 0.06 microgram ml-1 BAL. This level is significantly lower that the level of DPPC determined in BAL from five normal volunteers 2.48 +/- 0.40 micrograms ml-1. At day 0, the BAL level of DPPC in patients treated with methylprednisolone was not different from the BAL level of DPPC in patients not treated with methylprednisolone. By day 10 of therapy for P. carinii pneumonia, BAL levels of DPPC in all patients had increased to 1.05 +/- 0.19 micrograms ml-1 BAL. At day 10 DPPC levels in the methylprednisolone treated group were not different from the group not treated with methylprednisolone. We conclude that in HIV-infected patients, lung surfactant lipid is reduced in the setting of P. carinii pneumonia. The lipid levels return toward normal levels with treatment. Adjuvant therapy with corticosteroids does not alter the rate of recovery of surfactant lipid levels at least after 10 days of therapy.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1999

Hormone replacement therapy: patterns of use studied through British general practice computerized records.

OBJECTIVE: We aimed to describe the longitudinal pattern of hormone replacement therapy (HRT) consumption in a cohort of long-term users (defined as use for >1 year). METHOD: We carried out longitudinal analysis of prescription data derived from GPs' computer records. Subjects were recruited through 15 general practices in the former Oxford, South West and North West Thames Regions that contributed to the VAMP/OPCS general practice research database. All women in the practices aged 45-64 years in September 1991 were identified. Of these, the analysis concerned the 1224 long-term users and 1154 non-user controls who remained in the practices from September 1991 to March 1995; 868 (71%) of the users and 698 (61%) of the controls also provided questionnaire data. RESULTS: The prevalence of HRT use was 15% in 1992, a rise of 16% from 1991. The prevalence of long-term use was 10%; 22% of the cohort identified as taking HRT between April and September 1991 had left the practices or were not taking HRT 1 year later. But for the group defined as long-term users in 1992, the rate of discontinuation was less than 5% per year over the following 2 1/2 years. Users of opposed therapy were 50% more likely to discontinue than users of unopposed therapy. Almost all women who had or had not undergone hysterectomy were taking unopposed or opposed therapy, respectively. Over 80% of prescriptions were for oral therapy. A third of users of either opposed or unopposed therapy changed the formulation during the 4 years of observation, and two-thirds of those who used both forms changed at least once in addition. Two changes were required to accommodate 94% of users. CONCLUSIONS: Once women have taken HRT for a year, their continuation rate is over 95% per annum. Although the majority of women stayed with one formulation, a substantial minority changed formulation quite frequently, three formulations being required to accommodate 94% of long-term users over 4 years. Any trial of HRT use will need to recruit long-term users and allow for change in formulation of HRT in its protocol.

Aged↗
PubMed1998

Stuttering: a brief review.

The etiology of stuttering is controversial. The prevailing theories point to measurable neurophysical dysfunctions that disrupt the precise timing required to produce speech. Stuttering is a common disorder that usually resolves by adulthood. Almost 80 percent of children who stutter recover fluency by the age of 16 years. Mild stuttering is self-limited, but more severe stuttering requires speech therapy which is the mainstay of treatment. Delayed auditory feedback and computer-assisted training are currently used to help slow down speech and control other speech mechanisms. Pharmacologic therapy is seldom used, although haloperidol has been somewhat effective.

Haloperidol↗
PubMed1998

Teaching the theory behind guidelines: the Royal College of General Practitioners Guidelines Skills Course.

In the face of a perceived lack of widespread understanding of the theoretical issues underlying the development, dissemination and implementation of clinical guidelines, the Royal College of General Practitioners Guidelines Group developed a 2-day course aimed at teaching the theory in these areas. The course was targeted at potential opinion formers and ran on six occasions. Postal questionnaire assessment of the course revealed high levels of satisfaction with all aspects of the course and high levels of reported use of the knowledge gained. Further developments of the course are discussed.

Clinical Competence↗
PubMed1998

Functional foods and health claims: a public health policy perspective.

OBJECTIVE: To propose a policy framework for the regulation of functional foods and health claims within a public health context. DESIGN: This article reviews the empirical evidence and public health principles associated with functional foods and health claims to analyse the issues, challenge the assumptions that have emerged and explore options for moving forward. SETTING: Functional foods and health claims are among the more controversial and complex issues being debated by food regulators internationally. Proponents of functional foods and health claims state that functional foods may reduce health care expenditure and health claims are a legitimate nutrition education tool that will help them inform consumers of the health benefits of certain food products. Conversely, opponents of these developments respond that it is the total diet that is important for health, not so-called 'magic bullets'. Moreover, they argue that health claims will enable manufacturers to indulge in marketing hyperbole and essentially blur the distinction between food and drugs. This topic provides a valuable case study of public policy in relation to food and health. CONCLUSION: The need to maintain a general prohibition on health claims while accommodating specific exemptions supported by scientific substantiation is recommended. Nutrition education and monitoring and evaluation are integral to the proposed regulatory framework. The intention of this policy position is to encourage research and development of innovative food products while avoiding an inappropriate medicalization of the general food supply.

Food, Organic↗
PubMed1997

Efficacy of inhaled fluticasone propionate in asthma results from topical and not from systemic activity.

The objective of this study was to determine whether the therapeutic benefits of inhaled fluticasone propionate are mediated through topical or systemic effects. Two hundred seventy-four patients with asthma receiving beclomethasone dipropionate or triamcinolone acetonide during a 2-wk, single-blind, run-in period were randomized to inhaled fluticasone propionate powder 100 or 500 micrograms twice daily, oral fluticasone propionate 20 mg once daily, or placebo during a 6-wk treatment period. Patients receiving inhaled fluticasone propionate had a significantly greater probability of remaining in the study over time compared with patients receiving oral fluticasone propionate or placebo (p = 0.001). FEV1 and PEF rates at end point were significantly higher with inhaled fluticasone propionate treatment regimens than with oral fluticasone propionate (with the exception of PEF rates for inhaled fluticasone propionate 100 micrograms) or placebo treatments (p < or = 0.004). Systemic exposure to fluticasone propionate as assessed by trough plasma concentrations and/or 12-hr plasma concentration area under the curve analyses (AUC12) was higher with the oral fluticasone propionate than with the two inhaled fluticasone propionate treatment groups. The results of this study suggest that the therapeutic benefits of inhaled fluticasone propionate are mediated through topical effects in the lungs and not through systemic effects.

Administration, Inhalation↗