A. Fraser - Academia.edu (original) (raw)

Papers by A. Fraser

Journal of General Microbiology, 1956

The distribution of adapted particles of Vi-phage I1 has been examined. Fluctuation tests in whic... more The distribution of adapted particles of Vi-phage I1 has been examined. Fluctuation tests in which phage A was grown for a single cycle in type A of Salmonella typhi showed that phage E 1 particles conformed to a Poisson distribution in a series of small samples and cannot, therefore, be spontaneous mutants of phage A. Particles of phage D 1, on the other hand, showed a clonal distribution in a similar series of samples and are thus spontaneous host-range mutants of phage A. Phage El reverted to phage A during a single cycle of growth in type A organisms, which confirms that phage E 1 is a phenotypic modification of phage A. In contrast, phage D1 was unaltered by a single cycle of propagation in type A organisms and its mutant nature is thus verified. Phage 29 has also been shown to be a host-range mutant of Vi-phage 11. The adsorption of phage A to type E 1 is lethal to the bacteria, of which only a small proportion support phage growth. The general applicability of these findings to the numerous adaptations of Vi-phage I1 is discussed.

The clinical presentation of autonomic failure is orthostatic hypotension. Severely affected pati... more The clinical presentation of autonomic failure is orthostatic hypotension. Severely affected patients require pharmacological treatment to prevent presyncopal symptoms or frank syncope. We previously reported in a proof of concept study that pediatric doses of the norepinephrine transporter blockade, atomoxetine, increases blood pressure in autonomic failure patients with residual sympathetic activity compared with placebo. Given that the sympathetic nervous system is maximally activated in the upright position, we hypothesized that atomoxetine would be superior to midodrine, a direct vasoconstrictor, in improving upright blood pressure and orthostatic hypotension-related symptoms. To test this hypothesis, we compared the effect of acute atomoxetine versus midodrine on upright systolic blood pressure and orthostatic symptom scores in 65 patients with severe autonomic failure. There were no differences in seated systolic blood pressure (means difference=0.3 mm Hg; 95% confidence interval, −7.3 to 7.9; P=0.94). In contrast, atomoxetine produced a greater pressor response in upright systolic blood pressure (means difference=7.5 mm Hg; 95% confidence interval, 0.6-15; P=0.03) compared with midodrine. Furthermore, atomoxetine (means difference=0.4; 95% confidence interval, 0.1-0.8; P=0.02), but not midodrine (means difference=0.5; 95% confidence interval, −0.1 to 1.0; P=0.08), improved orthostatic hypotension-related symptoms as compared with placebo. The results of our study suggest that atomoxetine could be a superior therapeutic option than midodrine for the treatment of orthostatic hypotension in autonomic failure.

PLoS ONE, 2010

Background: Increasing evidence suggests a role for mineral metabolism in cardiovascular disease ... more Background: Increasing evidence suggests a role for mineral metabolism in cardiovascular disease risk. 25-hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH), and calcium may be directly associated with cardiovascular risk factors or mediated by each other. Methodology/Principal Findings: We combined data for adult participants in three cycles of the National Health and Nutrition Examination Survey (2001-2, 2003-4, 2005-6), a representative sample of the civilian, non-institutionalized US population (N = 3,958). Using this data we examined joint associations of 25(OH)D, PTH and calcium with a range of cardiovascular risk factors. 25(OH)D was inversely associated with fasting insulin (mean difference in insulin per 1 standard deviation 25(OH)D: 20.053 (95%CI: 20.091, 20.015)), glucose (20.046 95%CI: 20.081, 20.012) and systolic blood pressure (SBP) (20.032 95%CI: 20.062, 20.001), and positively associated with high density lipoprotein cholesterol HDL-c (0.088 95%CI: 0.044, 0.148), after adjustment for ethnicity, smoking, socioeconomic status and waist circumference. PTH was positively associated with diastolic blood pressure (0.110, 95%CI: 0.055, 0.164) in confounder adjusted models, but was not associated with other cardiovascular risk factors. Albumin adjusted calcium was associated with triglycerides (0.

PLoS ONE, 2013

Objectives: Epidemiological evidence for associations of Anti-Mü llerian hormone (AMH) with cardi... more Objectives: Epidemiological evidence for associations of Anti-Mü llerian hormone (AMH) with cardiometabolic risk factors is lacking. Existing evidence comes from small studies in select adult populations, and findings are conflicting. We aimed to assess whether AMH is associated with cardiometabolic risk factors in a general population of adolescent females. Methods: AMH, fasting insulin, glucose, HDLc, LDLc, triglycerides and C-reactive protein (CRP) were measured at a mean age 15.5 years in 1,308 female participants in the Avon Longitudinal Study of Parents and Children (ALSPAC). Multivariable linear regression was used to examine associations of AMH with these cardiometabolic outcomes. Results: AMH values ranged from 0.16-35.84 ng/ml and median AMH was 3.57 ng/ml (IQR: 2.41, 5.49). For females classified as post-pubertal (n = 848) at the time of assessment median (IQR) AMH was 3.81 ng/ml (2.55, 5.82) compared with 3.25 ng/ ml (2.23, 5.05) in those classed as early pubertal (n = 460, P#0.001). After adjusting for birth weight, gestational age, pubertal stage, age, ethnicity, socioeconomic position, adiposity and use of hormonal contraceptives, there were no associations with any of the cardiometabolic outcomes. For example fasting insulin changed by 0% per doubling of AMH (95%CI: 23%,+2%) p = 0.70, with identical results if HOMA-IR was used. Results were similar after additional adjustment for smoking, physical activity and age at menarche, after exclusion of 3% of females with the highest AMH values, after excluding those that had not started menarche and after excluding those using hormonal contraceptives. Conclusion: Our results suggest that in healthy adolescent females, AMH is not associated with cardiometabolic risk factors.

International Journal of Epidemiology, 2012

The Avon Longitudinal Study of Children and Parents (ALSPAC) was established to understand how ge... more The Avon Longitudinal Study of Children and Parents (ALSPAC) was established to understand how genetic and environmental characteristics influence health and development in parents and children. All pregnant women resident in a defined area in the South West of England, with an expected date of delivery between 1st April 1991 and 31st December 1992, were eligible and 13 761 women (contributing 13 867 pregnancies) were recruited. These women have been followed over the last 19-22 years and have completed up to 20 questionnaires, have had detailed data abstracted from their medical records and have information on any cancer diagnoses and deaths through record linkage. A follow-up assessment was completed 17-18 years postnatal at which anthropometry, blood pressure, fat, lean and bone mass and carotid intima media thickness were assessed, and a fasting blood sample taken. The second follow-up clinic, which additionally measures cognitive function, physical capability, physical activity (with accelerometer) and wrist bone architecture, is underway and two further assessments with similar measurements will take place over the next 5 years. There is a detailed biobank that includes DNA, with genome-wide data available on 410 000, stored serum and plasma taken repeatedly since pregnancy and other samples; a wide range of data on completed biospecimen assays are available. Details of how to access these data are provided in this cohort profile.

Epidemiology, 2013

Methods for the assessment of changes in dietary intake across the life course are underdeveloped... more Methods for the assessment of changes in dietary intake across the life course are underdeveloped. We demonstrate the use of linear-spline multilevel models to summarize energy-intake trajectories through childhood and adolescence and their application as exposures, outcomes, or mediators. The Avon Longitudinal Study of Parents and Children assessed children's dietary intake several times between ages 3 and 13 years, using both food frequency questionnaires (FFQs) and 3-day food diaries. We estimated energy-intake trajectories for 12,032 children using linear-spline multilevel models. We then assessed the associations of these trajectories with maternal body mass index (BMI), and later offspring BMI, and also their role in mediating the relation between maternal and offspring BMIs. Models estimated average and individual energy intake at 3 years, and linear changes in energy intake from age 3 to 7 years and from age 7 to 13 years. By including the exposure (in this example, maternal BMI) in the multilevel model, we were able to estimate the average energy-intake trajectories across levels of the exposure. When energy-intake trajectories are the exposure for a later outcome (in this case offspring BMI) or a mediator (between maternal and offspring BMI), results were similar, whether using a two-step process (exporting individual-level intercepts and slopes from multilevel models and using these in linear regression/path analysis), or a single-step process (multivariate multilevel models). Trajectories were similar when FFQs and food diaries were assessed either separately, or when combined into one model. Linear-spline multilevel models provide useful summaries of trajectories of dietary intake that can be used as an exposure, outcome, or mediator.

Diabetologia, 2008

Aim The aim of the study was to compare the effect of different dietary interventions on alanine ... more Aim The aim of the study was to compare the effect of different dietary interventions on alanine aminotransferase (ALT) in obese patients with diabetes. Methods A post hoc analysis of an open label, parallel design, quasi-randomised (allocation by alternation), controlled trial, conducted in Israel. Obese patients with diabetes (n=259), treated in the community, were centrally allocated to one of three diets: (1) the 2003 recommended American Diabetes Association diet (ADA): 50-55% carbohydrate, 30% fat and 20% protein, n=85; (2) a low glycaemic index (LGI) diet: 50-55% LGI carbohydrate, 30% fat, 15-20% protein, n = 89; or (3) a modified Mediterranean diet (MMD): 35% LGI carbohydrate, 45% fat that was high in monounsaturated fat, 15-20% protein, n=85. ALT was measured at 6 and 12 months. Results ALT levels decreased in all arms; however, the MMD was associated with the lowest ALT levels at month 6 (n=201: ADA n=64, LGI n=73, MMD n=64) and month 12 of follow-up (n=179). At 12 months mean ALT levels were 19.8±1.4 U/l in the ADA diet arm (n=54), 18.0±1.5 U/l in the LGI diet arm (n=64) and 14.4±1.7 in the MMD arm (n=61, p<0.001). Evidence for an effect of diet on ALT levels persisted when controlling for post-randomisation changes in waist to hip ratio, BMI, homeostasis model assessment (HOMA) or triacylglycerol. Conclusions A Mediterranean diet may have a beneficial effect on liver steatosis in obese patients with diabetes. Results of trials assessing the effect of dietary composition on clinical outcomes should be awaited before a decisive conclusion can be reached. In addition to clinical outcomes, such studies should address the issue of primary prevention of steatosis in high-risk and healthy individuals.

Diabetologia, 2009

Aims/hypothesis The aim of the study was to examine the association of existing diabetes (i.e. al... more Aims/hypothesis The aim of the study was to examine the association of existing diabetes (i.e. already diagnosed prior to pregnancy), gestational diabetes and glycosuria (both diagnosed and ascertained during pregnancy) with birthweight and future offspring BMI, waist circumference and fat mass (assessed by dual x-ray emission absorptiometry).

Arteriosclerosis, Thrombosis, and Vascular Biology, 2007

Objective— To investigate the association of γ-glutamyltransferase (GGT) with incident CHD and st... more Objective— To investigate the association of γ-glutamyltransferase (GGT) with incident CHD and stroke. GGT is a marker of alcohol intake but may also reflect oxidative stress and nonalcoholic fatty liver disease. Alanine aminotransferase (ALT) is the enzyme most closely associated with liver fat content. Methods and Results— Associations of GGT and ALT with incident CHD, stroke, and a combined outcome of CHD or stroke were examined in the British Women’s Heart and Health study (n=2961), and a meta-analysis of population based studies examining these associations was performed. In pooled analyses of fully adjusted results of 10 prospective studies, a change of 1 U/L of GGT was associated with a HR=1.20 (95% CI: 1.02, 1.40) for CHD; a HR=1.54 (95% CI: 1.20, 2.00) for stroke; and HR=1.34 (95% CI: 1.22, 1.48) for CHD or stroke. Heterogeneity was substantially decreased when 2 studies in Asian populations were excluded. In a subgroup of nondrinkers results were similar to the main analys...

The American Journal of Medicine, 2006

We evaluated the effect of inappropriate antibiotic treatment on mortality and duration of hospit... more We evaluated the effect of inappropriate antibiotic treatment on mortality and duration of hospital stay in medical inpatients with bacterial infections. SUBJECTS AND METHODS: Two cohorts of febrile adult patients (excluding patients with acquired immune deficiency syndrome and organ transplant recipients), hospitalized in three medical centers in Israel, Italy, and Germany, were included. Patients' data were collected prospectively. Initial empirical treatment was defined as appropriate if an antibiotic prescribed within 24 hours of the first encounter with the patient matched the in vitro susceptibility of a pathogen deemed to be the likely cause of infection. The results of cultures and serologic or direct tests, and data on outcomes were collected 30 days after initiation of empirical treatment. RESULTS: A total of 920 patients (26% of 3529 included patients) had microbiologically documented infections, and mortality data were available for 895 patients (97%). Inappropriate initial antibiotic treatment was prescribed in 36% of patients (N ϭ 319). All-cause 30-day mortality rates were 20.1% (N ϭ 64) and 11.8% (N ϭ 68) in patients who received inappropriate and appropriate treatment, respectively (odds ratio ϭ 1.88, 95% confidence interval [CI], 1.29-2.72, P ϭ .001). When adjustment was made for medical center and other variables, the association between inappropriate with mortality was significant (odds ratio ϭ 1.58, 95% CI, 0.99-2.54, P ϭ .058). In all 3 medical centers, the mean duration of hospital stay was at least 2 days longer for patients who were prescribed inappropriate antibiotic treatment (overall P ϭ .002). This association was consistent after adjusting for other variables (P ϭ .006). CONCLUSION: Appropriate empirical antibiotic treatment is associated with a better survival and shortened duration of hospital stay in medical patients with bacterial infections.

International Journal of Antimicrobial Agents, 2007

This study sought to compare the efficacy and adverse effects of any aminoglycoside as a single a... more This study sought to compare the efficacy and adverse effects of any aminoglycoside as a single antibiotic with other antibiotics for the treatment of patients with infection. Methods: Systematic review of the literature and meta-analysis. We searched for randomized controlled trials comparing the efficacy of single aminoglycoside antibiotic treatment with one or more nonaminoglycoside antibiotic for patients with infection in the Cochrane Library, MEDLINE, EMBASE, LILACS, databases of ongoing trials and conference proceedings. Two reviewers assessed trial eligibility, quality and extracted data. Pooled relative risks (RR) with 95% confidence intervals (CI) were calculated for dichotomous data. Results: The search yielded 37 trials of which 26 included patients with urinary tract infection. Aminoglycosides were equally effective as comparators in the analysis of the primary outcomes, allcause mortality (RR 1.11, 95% CI 0.68, 1.81, 9 trials, 503 patients) and treatment failure (RR 1.10, 95% CI 0.96, 1.27, 32 trials, 1890 patients). Aminoglycosides were associated with a significantly higher rate of bacteriological failure at end of therapy (RR 1.44, 95% CI 1.21, 1.72, 27 trials, 1668 patients). Subgroup analyses according to quality of trial, type of antibiotics, source of infection and rate of clinical sepsis did not alter the outcomes. Less adverse effects in total but more nephrotoxic effects were observed in patients treated with aminoglycosides. Conclusions: The present data support the use of aminoglycosides for urinary tract infections. The paucity of trials including patients with sepsis or reporting on mortality precludes firm recommendations for patients with infections other than of the urinary tract.

International Journal of Antimicrobial Agents, 2007

Objectives: This study sought to compare the efficacy and adverse effects of any aminoglycoside a... more Objectives: This study sought to compare the efficacy and adverse effects of any aminoglycoside as a single antibiotic with other antibiotics for the treatment of patients with infection.

Journal of General Microbiology, 1956

The distribution of adapted particles of Vi-phage I1 has been examined. Fluctuation tests in whic... more The distribution of adapted particles of Vi-phage I1 has been examined. Fluctuation tests in which phage A was grown for a single cycle in type A of Salmonella typhi showed that phage E 1 particles conformed to a Poisson distribution in a series of small samples and cannot, therefore, be spontaneous mutants of phage A. Particles of phage D 1, on the other hand, showed a clonal distribution in a similar series of samples and are thus spontaneous host-range mutants of phage A. Phage El reverted to phage A during a single cycle of growth in type A organisms, which confirms that phage E 1 is a phenotypic modification of phage A. In contrast, phage D1 was unaltered by a single cycle of propagation in type A organisms and its mutant nature is thus verified. Phage 29 has also been shown to be a host-range mutant of Vi-phage 11. The adsorption of phage A to type E 1 is lethal to the bacteria, of which only a small proportion support phage growth. The general applicability of these findings to the numerous adaptations of Vi-phage I1 is discussed.

The clinical presentation of autonomic failure is orthostatic hypotension. Severely affected pati... more The clinical presentation of autonomic failure is orthostatic hypotension. Severely affected patients require pharmacological treatment to prevent presyncopal symptoms or frank syncope. We previously reported in a proof of concept study that pediatric doses of the norepinephrine transporter blockade, atomoxetine, increases blood pressure in autonomic failure patients with residual sympathetic activity compared with placebo. Given that the sympathetic nervous system is maximally activated in the upright position, we hypothesized that atomoxetine would be superior to midodrine, a direct vasoconstrictor, in improving upright blood pressure and orthostatic hypotension-related symptoms. To test this hypothesis, we compared the effect of acute atomoxetine versus midodrine on upright systolic blood pressure and orthostatic symptom scores in 65 patients with severe autonomic failure. There were no differences in seated systolic blood pressure (means difference=0.3 mm Hg; 95% confidence interval, −7.3 to 7.9; P=0.94). In contrast, atomoxetine produced a greater pressor response in upright systolic blood pressure (means difference=7.5 mm Hg; 95% confidence interval, 0.6-15; P=0.03) compared with midodrine. Furthermore, atomoxetine (means difference=0.4; 95% confidence interval, 0.1-0.8; P=0.02), but not midodrine (means difference=0.5; 95% confidence interval, −0.1 to 1.0; P=0.08), improved orthostatic hypotension-related symptoms as compared with placebo. The results of our study suggest that atomoxetine could be a superior therapeutic option than midodrine for the treatment of orthostatic hypotension in autonomic failure.

PLoS ONE, 2010

Background: Increasing evidence suggests a role for mineral metabolism in cardiovascular disease ... more Background: Increasing evidence suggests a role for mineral metabolism in cardiovascular disease risk. 25-hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH), and calcium may be directly associated with cardiovascular risk factors or mediated by each other. Methodology/Principal Findings: We combined data for adult participants in three cycles of the National Health and Nutrition Examination Survey (2001-2, 2003-4, 2005-6), a representative sample of the civilian, non-institutionalized US population (N = 3,958). Using this data we examined joint associations of 25(OH)D, PTH and calcium with a range of cardiovascular risk factors. 25(OH)D was inversely associated with fasting insulin (mean difference in insulin per 1 standard deviation 25(OH)D: 20.053 (95%CI: 20.091, 20.015)), glucose (20.046 95%CI: 20.081, 20.012) and systolic blood pressure (SBP) (20.032 95%CI: 20.062, 20.001), and positively associated with high density lipoprotein cholesterol HDL-c (0.088 95%CI: 0.044, 0.148), after adjustment for ethnicity, smoking, socioeconomic status and waist circumference. PTH was positively associated with diastolic blood pressure (0.110, 95%CI: 0.055, 0.164) in confounder adjusted models, but was not associated with other cardiovascular risk factors. Albumin adjusted calcium was associated with triglycerides (0.

PLoS ONE, 2013

Objectives: Epidemiological evidence for associations of Anti-Mü llerian hormone (AMH) with cardi... more Objectives: Epidemiological evidence for associations of Anti-Mü llerian hormone (AMH) with cardiometabolic risk factors is lacking. Existing evidence comes from small studies in select adult populations, and findings are conflicting. We aimed to assess whether AMH is associated with cardiometabolic risk factors in a general population of adolescent females. Methods: AMH, fasting insulin, glucose, HDLc, LDLc, triglycerides and C-reactive protein (CRP) were measured at a mean age 15.5 years in 1,308 female participants in the Avon Longitudinal Study of Parents and Children (ALSPAC). Multivariable linear regression was used to examine associations of AMH with these cardiometabolic outcomes. Results: AMH values ranged from 0.16-35.84 ng/ml and median AMH was 3.57 ng/ml (IQR: 2.41, 5.49). For females classified as post-pubertal (n = 848) at the time of assessment median (IQR) AMH was 3.81 ng/ml (2.55, 5.82) compared with 3.25 ng/ ml (2.23, 5.05) in those classed as early pubertal (n = 460, P#0.001). After adjusting for birth weight, gestational age, pubertal stage, age, ethnicity, socioeconomic position, adiposity and use of hormonal contraceptives, there were no associations with any of the cardiometabolic outcomes. For example fasting insulin changed by 0% per doubling of AMH (95%CI: 23%,+2%) p = 0.70, with identical results if HOMA-IR was used. Results were similar after additional adjustment for smoking, physical activity and age at menarche, after exclusion of 3% of females with the highest AMH values, after excluding those that had not started menarche and after excluding those using hormonal contraceptives. Conclusion: Our results suggest that in healthy adolescent females, AMH is not associated with cardiometabolic risk factors.

International Journal of Epidemiology, 2012

The Avon Longitudinal Study of Children and Parents (ALSPAC) was established to understand how ge... more The Avon Longitudinal Study of Children and Parents (ALSPAC) was established to understand how genetic and environmental characteristics influence health and development in parents and children. All pregnant women resident in a defined area in the South West of England, with an expected date of delivery between 1st April 1991 and 31st December 1992, were eligible and 13 761 women (contributing 13 867 pregnancies) were recruited. These women have been followed over the last 19-22 years and have completed up to 20 questionnaires, have had detailed data abstracted from their medical records and have information on any cancer diagnoses and deaths through record linkage. A follow-up assessment was completed 17-18 years postnatal at which anthropometry, blood pressure, fat, lean and bone mass and carotid intima media thickness were assessed, and a fasting blood sample taken. The second follow-up clinic, which additionally measures cognitive function, physical capability, physical activity (with accelerometer) and wrist bone architecture, is underway and two further assessments with similar measurements will take place over the next 5 years. There is a detailed biobank that includes DNA, with genome-wide data available on 410 000, stored serum and plasma taken repeatedly since pregnancy and other samples; a wide range of data on completed biospecimen assays are available. Details of how to access these data are provided in this cohort profile.

Epidemiology, 2013

Methods for the assessment of changes in dietary intake across the life course are underdeveloped... more Methods for the assessment of changes in dietary intake across the life course are underdeveloped. We demonstrate the use of linear-spline multilevel models to summarize energy-intake trajectories through childhood and adolescence and their application as exposures, outcomes, or mediators. The Avon Longitudinal Study of Parents and Children assessed children&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s dietary intake several times between ages 3 and 13 years, using both food frequency questionnaires (FFQs) and 3-day food diaries. We estimated energy-intake trajectories for 12,032 children using linear-spline multilevel models. We then assessed the associations of these trajectories with maternal body mass index (BMI), and later offspring BMI, and also their role in mediating the relation between maternal and offspring BMIs. Models estimated average and individual energy intake at 3 years, and linear changes in energy intake from age 3 to 7 years and from age 7 to 13 years. By including the exposure (in this example, maternal BMI) in the multilevel model, we were able to estimate the average energy-intake trajectories across levels of the exposure. When energy-intake trajectories are the exposure for a later outcome (in this case offspring BMI) or a mediator (between maternal and offspring BMI), results were similar, whether using a two-step process (exporting individual-level intercepts and slopes from multilevel models and using these in linear regression/path analysis), or a single-step process (multivariate multilevel models). Trajectories were similar when FFQs and food diaries were assessed either separately, or when combined into one model. Linear-spline multilevel models provide useful summaries of trajectories of dietary intake that can be used as an exposure, outcome, or mediator.

Diabetologia, 2008

Aim The aim of the study was to compare the effect of different dietary interventions on alanine ... more Aim The aim of the study was to compare the effect of different dietary interventions on alanine aminotransferase (ALT) in obese patients with diabetes. Methods A post hoc analysis of an open label, parallel design, quasi-randomised (allocation by alternation), controlled trial, conducted in Israel. Obese patients with diabetes (n=259), treated in the community, were centrally allocated to one of three diets: (1) the 2003 recommended American Diabetes Association diet (ADA): 50-55% carbohydrate, 30% fat and 20% protein, n=85; (2) a low glycaemic index (LGI) diet: 50-55% LGI carbohydrate, 30% fat, 15-20% protein, n = 89; or (3) a modified Mediterranean diet (MMD): 35% LGI carbohydrate, 45% fat that was high in monounsaturated fat, 15-20% protein, n=85. ALT was measured at 6 and 12 months. Results ALT levels decreased in all arms; however, the MMD was associated with the lowest ALT levels at month 6 (n=201: ADA n=64, LGI n=73, MMD n=64) and month 12 of follow-up (n=179). At 12 months mean ALT levels were 19.8±1.4 U/l in the ADA diet arm (n=54), 18.0±1.5 U/l in the LGI diet arm (n=64) and 14.4±1.7 in the MMD arm (n=61, p<0.001). Evidence for an effect of diet on ALT levels persisted when controlling for post-randomisation changes in waist to hip ratio, BMI, homeostasis model assessment (HOMA) or triacylglycerol. Conclusions A Mediterranean diet may have a beneficial effect on liver steatosis in obese patients with diabetes. Results of trials assessing the effect of dietary composition on clinical outcomes should be awaited before a decisive conclusion can be reached. In addition to clinical outcomes, such studies should address the issue of primary prevention of steatosis in high-risk and healthy individuals.

Diabetologia, 2009

Aims/hypothesis The aim of the study was to examine the association of existing diabetes (i.e. al... more Aims/hypothesis The aim of the study was to examine the association of existing diabetes (i.e. already diagnosed prior to pregnancy), gestational diabetes and glycosuria (both diagnosed and ascertained during pregnancy) with birthweight and future offspring BMI, waist circumference and fat mass (assessed by dual x-ray emission absorptiometry).

Arteriosclerosis, Thrombosis, and Vascular Biology, 2007

Objective— To investigate the association of γ-glutamyltransferase (GGT) with incident CHD and st... more Objective— To investigate the association of γ-glutamyltransferase (GGT) with incident CHD and stroke. GGT is a marker of alcohol intake but may also reflect oxidative stress and nonalcoholic fatty liver disease. Alanine aminotransferase (ALT) is the enzyme most closely associated with liver fat content. Methods and Results— Associations of GGT and ALT with incident CHD, stroke, and a combined outcome of CHD or stroke were examined in the British Women’s Heart and Health study (n=2961), and a meta-analysis of population based studies examining these associations was performed. In pooled analyses of fully adjusted results of 10 prospective studies, a change of 1 U/L of GGT was associated with a HR=1.20 (95% CI: 1.02, 1.40) for CHD; a HR=1.54 (95% CI: 1.20, 2.00) for stroke; and HR=1.34 (95% CI: 1.22, 1.48) for CHD or stroke. Heterogeneity was substantially decreased when 2 studies in Asian populations were excluded. In a subgroup of nondrinkers results were similar to the main analys...

The American Journal of Medicine, 2006

We evaluated the effect of inappropriate antibiotic treatment on mortality and duration of hospit... more We evaluated the effect of inappropriate antibiotic treatment on mortality and duration of hospital stay in medical inpatients with bacterial infections. SUBJECTS AND METHODS: Two cohorts of febrile adult patients (excluding patients with acquired immune deficiency syndrome and organ transplant recipients), hospitalized in three medical centers in Israel, Italy, and Germany, were included. Patients' data were collected prospectively. Initial empirical treatment was defined as appropriate if an antibiotic prescribed within 24 hours of the first encounter with the patient matched the in vitro susceptibility of a pathogen deemed to be the likely cause of infection. The results of cultures and serologic or direct tests, and data on outcomes were collected 30 days after initiation of empirical treatment. RESULTS: A total of 920 patients (26% of 3529 included patients) had microbiologically documented infections, and mortality data were available for 895 patients (97%). Inappropriate initial antibiotic treatment was prescribed in 36% of patients (N ϭ 319). All-cause 30-day mortality rates were 20.1% (N ϭ 64) and 11.8% (N ϭ 68) in patients who received inappropriate and appropriate treatment, respectively (odds ratio ϭ 1.88, 95% confidence interval [CI], 1.29-2.72, P ϭ .001). When adjustment was made for medical center and other variables, the association between inappropriate with mortality was significant (odds ratio ϭ 1.58, 95% CI, 0.99-2.54, P ϭ .058). In all 3 medical centers, the mean duration of hospital stay was at least 2 days longer for patients who were prescribed inappropriate antibiotic treatment (overall P ϭ .002). This association was consistent after adjusting for other variables (P ϭ .006). CONCLUSION: Appropriate empirical antibiotic treatment is associated with a better survival and shortened duration of hospital stay in medical patients with bacterial infections.

International Journal of Antimicrobial Agents, 2007

This study sought to compare the efficacy and adverse effects of any aminoglycoside as a single a... more This study sought to compare the efficacy and adverse effects of any aminoglycoside as a single antibiotic with other antibiotics for the treatment of patients with infection. Methods: Systematic review of the literature and meta-analysis. We searched for randomized controlled trials comparing the efficacy of single aminoglycoside antibiotic treatment with one or more nonaminoglycoside antibiotic for patients with infection in the Cochrane Library, MEDLINE, EMBASE, LILACS, databases of ongoing trials and conference proceedings. Two reviewers assessed trial eligibility, quality and extracted data. Pooled relative risks (RR) with 95% confidence intervals (CI) were calculated for dichotomous data. Results: The search yielded 37 trials of which 26 included patients with urinary tract infection. Aminoglycosides were equally effective as comparators in the analysis of the primary outcomes, allcause mortality (RR 1.11, 95% CI 0.68, 1.81, 9 trials, 503 patients) and treatment failure (RR 1.10, 95% CI 0.96, 1.27, 32 trials, 1890 patients). Aminoglycosides were associated with a significantly higher rate of bacteriological failure at end of therapy (RR 1.44, 95% CI 1.21, 1.72, 27 trials, 1668 patients). Subgroup analyses according to quality of trial, type of antibiotics, source of infection and rate of clinical sepsis did not alter the outcomes. Less adverse effects in total but more nephrotoxic effects were observed in patients treated with aminoglycosides. Conclusions: The present data support the use of aminoglycosides for urinary tract infections. The paucity of trials including patients with sepsis or reporting on mortality precludes firm recommendations for patients with infections other than of the urinary tract.

International Journal of Antimicrobial Agents, 2007

Objectives: This study sought to compare the efficacy and adverse effects of any aminoglycoside a... more Objectives: This study sought to compare the efficacy and adverse effects of any aminoglycoside as a single antibiotic with other antibiotics for the treatment of patients with infection.