S. Fürst-Recktenwald - Academia.edu (original) (raw)

Uploads

Papers by S. Fürst-Recktenwald

BMJ Open Ophthalmology, 2017

et al. Oral administration of the 11bhydroxysteroiddehydrogenase type 1 inhibitor RO5093151 to pa... more et al. Oral administration of the 11bhydroxysteroiddehydrogenase type 1 inhibitor RO5093151 to patients with glaucoma: an adaptive, randomised, placebo-controlled clinical study.

Diabetes, Obesity and Metabolism, 2008

Aims: To compare the end-organ metabolic effects of insulin glulisine (glulisine), insulin lispro... more Aims: To compare the end-organ metabolic effects of insulin glulisine (glulisine), insulin lispro (lispro) and regular human insulin (RHI) in patients with type 1 diabetes mellitus. Methods: Eighteen patients with type 1 diabetes mellitus (mean age 36.9 AE 8.6 years, BMI 23.6 AE 2.8 kg/m 2 , haemoglobin A 1c 7.4 AE 0.9%) were randomized in this single-centre, double-blind, three-period cross-over, standard Latin-square, euglycaemic glucose clamp trial. Patients received sequential, primed stepwise intravenous infusions of glulisine, lispro or RHI (infusion rates were increased in a stepwise manner from an initial rate of 0.33 [180 min] to 0.66 [180 min] and 1.00 [180 min] mU/kg/min). The primary variables were the suppression of endogenous glucose production (S EGP) and glucose uptake (GU). Results: Mean basal endogenous glucose production (EGP) was 1.88, 2.12 and 2.12 mg/kg/min for glulisine, lispro and RHI respectively. Mean (AEs.e.) maximum absolute S EGP (adjusted for basal EGP) was À1.64 AE 0.06, À1.72 AE 0.05 and À1.56 AE 0.05 mg/kg/min respectively. Mean (AEs.e.) maximum absolute increase in GU (adjusted for basal GU) was 6.46 AE 0.26, 6.23 AE 0.24 and 6.72 AE 0.24 mg/kg/min respectively. There were no clinically relevant differences between the three insulin treatments with respect to serum insulin, free fatty acid (FFA), glycerol or lactate levels. No serious adverse events and no episodes of severe hypoglycaemia were reported. Conclusions: This study shows that glulisine, lispro and RHI have similar effects on S EGP , GU, FFA, glycerol and lactate levels, providing evidence for similar end-organ metabolic effects.

Diabetes, obesity & metabolism, 2014

We assessed safety and efficacy of two selective 11β-HSD1 inhibitors (RO5093151/RO-151 and RO5027... more We assessed safety and efficacy of two selective 11β-HSD1 inhibitors (RO5093151/RO-151 and RO5027383/RO-838) in this randomized, controlled study in metformin-treated patients with type 2 diabetes. Patients either received placebo (N = 21), RO-151 BID 5 mg (N = 24) or 200 mg (N = 20) or RO-838 QD 50 mg (N = 21) or 200 mg (N = 24) for 28 days. Metabolic assessments comprising of nine-point plasma glucose profiles, oral glucose tolerance tests and determination of metabolic biomarkers including insulin, C-peptide, glucagon, HbA1c and lipids were done at baseline and end of treatment. Despite the short treatment duration, both RO-151 and RO-838 showed trends for improved HbA1c and consistent reductions in body weight (-0.86 to -1.67 kg) exceeding those observed with placebo (-0.28 kg, p = 0.019 for 200 mg RO-151 vs. placebo). Insulin sensitivity parameters (e.g. HOMA-IR and Matsuda-Index) improved non-significantly with 200 mg RO-151. Lipid parameters did not consistently improve with ...

Journal of medical microbiology, 2000

Three Shiga toxin (Stx)-producing Escherichia coli (STEC) strains from patients with diarrhoea we... more Three Shiga toxin (Stx)-producing Escherichia coli (STEC) strains from patients with diarrhoea were identified, each of which contained three distinct stx genes (stx1, stx2 and stx2c). The strains belonged to the serotypes O52:H19, O75:H- and O157:H- and harboured eae and EHEC-hly sequences. Colony-blot immunoassay was used to demonstrate that both major types of Stx were expressed. The association of stx genes with either phage or phage DNA was demonstrated in all three strains. Isolated phage DNA from all strains contained stx1 sequences, but stx2 sequences were found only in phage DNA of two of these strains. The presence of three distinct stx genes may enhance the virulence of STEC strains and should be monitored. The observations demonstrate not only the potential of stx genes to spread within different serotypes, but also their capacity to accumulate within a single strain.

Guide to Paediatric Drug Development and Clinical Research, 2010

The lancet. Diabetes & endocrinology, 2014

The prevalence of non-alcoholic fatty liver disease is increasing worldwide and an effective and ... more The prevalence of non-alcoholic fatty liver disease is increasing worldwide and an effective and safe pharmacological treatment is needed. We investigated whether inhibition of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1, also known as HSD11B1) by RO5093151 could safely and effectively decrease liver-fat content in patients with this disorder. We did this phase 1b trial at four centres in Germany and Austria. Participants with non-alcoholic fatty liver disease (defined as (1)H magnetic resonance spectroscopy liver-fat content >5·56%), insulin resistance (homoeostatic model assessment of insulin resistance [HOMA-IR] of at least 2·0 mmol/L·mU/L), BMI greater than 27 kg/m(2), and aged 35-65 years were randomly assigned by interactive voice response system in a 1:1 ratio, stratified for triglyceride concentration (<1·7 mmol/L or ≥1·7 mmol/L), to oral RO5093151 (200 mg twice daily) or matching placebo for 12 weeks. The main exclusion criteria were other liver diseases, aspart...

Journal of Pediatric Endocrinology and Metabolism, 2000

Vocal disturbances in women with congenital adrenal hyperplasia and androgen excess should be ext... more Vocal disturbances in women with congenital adrenal hyperplasia and androgen excess should be extremely rare today since effective substitution with glucocorticoids is available. We present a 17 year-old female with congenital adrenal hyperplasia due to 21-hydroxylase deficiency and severe virilization because of long-term insufficient therapy. Laboratory data showed elevated serum levels of testosterone, 17-hydroxyprogesterone, plasma ACTH and a high excretion of urinary pregnanetriol. The phoniatric aspect showed a masculine voice. We discuss the different effects of androgens on the pubertal larynx and various hormonal disturbances that may cause voice changes as well as therapeutic options of voice therapy. From the pediatric point of view it might be important to perform a phoniatric examination in girls with congenital adrenal hyperplasia during puberty in order to monitor androgen effects.

The Journal of Clinical Pharmacology, 2012

This article aims to provide an overview of the current situation regarding pharmacogenetic and p... more This article aims to provide an overview of the current situation regarding pharmacogenetic and pharmacogenomic (PG) studies in pediatrics, with a special focus on the role of PG data in the regulatory decision-making process. Despite the gap in pharmacogenetic research due to the lack of translational studies in adults and children, several technologies exist in drug development and biomarkers validation, which could supply valuable information concerning labeling and dosing recommendations. If performed under strict good clinical practice quality criteria, such findings could be included in the submission package of new chemical entities and used as additional information for prescribers, supporting further evaluation and understanding of the efficacy and safety profile of new medicines. Even though regulatory authorities may be aware of the potential role of PG in medical practice and guidances are available about the integration of PG in drug development, most data obtained from PG studies are not used by prescribers. The challenge is to better understand whether PG markers can be used to assess potential differences in drug response during the clinical program, so PG data can be integrated into the regulatory decision-making process, enabling the introduction of labeling information that promotes optimal dosing in the pediatric population.

Diabetes, Obesity and Metabolism, 2008

To compare the end-organ metabolic effects of insulin glulisine (glulisine), insulin lispro (lisp... more To compare the end-organ metabolic effects of insulin glulisine (glulisine), insulin lispro (lispro) and regular human insulin (RHI) in patients with type 1 diabetes mellitus. Methods: Eighteen patients with type 1 diabetes mellitus (mean age 36.9 AE 8.6 years, BMI 23.6 AE 2.8 kg/m 2 , haemoglobin A 1c 7.4 AE 0.9%) were randomized in this single-centre, double-blind, three-period cross-over, standard Latin-square, euglycaemic glucose clamp trial. Patients received sequential, primed stepwise intravenous infusions of glulisine, lispro or RHI (infusion rates were increased in a stepwise manner from an initial rate of 0.33 [180 min] to 0.66 [180 min] and 1.00 [180 min] mU/kg/min). The primary variables were the suppression of endogenous glucose production (S EGP ) and glucose uptake (GU). Results: Mean basal endogenous glucose production (EGP) was 1.88, 2.12 and 2.12 mg/kg/min for glulisine, lispro and RHI respectively. Mean (AEs.e.) maximum absolute S EGP (adjusted for basal EGP) was À1.64 AE 0.06, À1.72 AE 0.05 and À1.56 AE 0.05 mg/kg/min respectively. Mean (AEs.e.) maximum absolute increase in GU (adjusted for basal GU) was 6.46 AE 0.26, 6.23 AE 0.24 and 6.72 AE 0.24 mg/kg/min respectively. There were no clinically relevant differences between the three insulin treatments with respect to serum insulin, free fatty acid (FFA), glycerol or lactate levels. No serious adverse events and no episodes of severe hypoglycaemia were reported. Conclusions: This study shows that glulisine, lispro and RHI have similar effects on S EGP , GU, FFA, glycerol and lactate levels, providing evidence for similar end-organ metabolic effects.

BMJ Open Ophthalmology, 2017

et al. Oral administration of the 11bhydroxysteroiddehydrogenase type 1 inhibitor RO5093151 to pa... more et al. Oral administration of the 11bhydroxysteroiddehydrogenase type 1 inhibitor RO5093151 to patients with glaucoma: an adaptive, randomised, placebo-controlled clinical study.

Diabetes, Obesity and Metabolism, 2008

Aims: To compare the end-organ metabolic effects of insulin glulisine (glulisine), insulin lispro... more Aims: To compare the end-organ metabolic effects of insulin glulisine (glulisine), insulin lispro (lispro) and regular human insulin (RHI) in patients with type 1 diabetes mellitus. Methods: Eighteen patients with type 1 diabetes mellitus (mean age 36.9 AE 8.6 years, BMI 23.6 AE 2.8 kg/m 2 , haemoglobin A 1c 7.4 AE 0.9%) were randomized in this single-centre, double-blind, three-period cross-over, standard Latin-square, euglycaemic glucose clamp trial. Patients received sequential, primed stepwise intravenous infusions of glulisine, lispro or RHI (infusion rates were increased in a stepwise manner from an initial rate of 0.33 [180 min] to 0.66 [180 min] and 1.00 [180 min] mU/kg/min). The primary variables were the suppression of endogenous glucose production (S EGP) and glucose uptake (GU). Results: Mean basal endogenous glucose production (EGP) was 1.88, 2.12 and 2.12 mg/kg/min for glulisine, lispro and RHI respectively. Mean (AEs.e.) maximum absolute S EGP (adjusted for basal EGP) was À1.64 AE 0.06, À1.72 AE 0.05 and À1.56 AE 0.05 mg/kg/min respectively. Mean (AEs.e.) maximum absolute increase in GU (adjusted for basal GU) was 6.46 AE 0.26, 6.23 AE 0.24 and 6.72 AE 0.24 mg/kg/min respectively. There were no clinically relevant differences between the three insulin treatments with respect to serum insulin, free fatty acid (FFA), glycerol or lactate levels. No serious adverse events and no episodes of severe hypoglycaemia were reported. Conclusions: This study shows that glulisine, lispro and RHI have similar effects on S EGP , GU, FFA, glycerol and lactate levels, providing evidence for similar end-organ metabolic effects.

Diabetes, obesity & metabolism, 2014

We assessed safety and efficacy of two selective 11β-HSD1 inhibitors (RO5093151/RO-151 and RO5027... more We assessed safety and efficacy of two selective 11β-HSD1 inhibitors (RO5093151/RO-151 and RO5027383/RO-838) in this randomized, controlled study in metformin-treated patients with type 2 diabetes. Patients either received placebo (N = 21), RO-151 BID 5 mg (N = 24) or 200 mg (N = 20) or RO-838 QD 50 mg (N = 21) or 200 mg (N = 24) for 28 days. Metabolic assessments comprising of nine-point plasma glucose profiles, oral glucose tolerance tests and determination of metabolic biomarkers including insulin, C-peptide, glucagon, HbA1c and lipids were done at baseline and end of treatment. Despite the short treatment duration, both RO-151 and RO-838 showed trends for improved HbA1c and consistent reductions in body weight (-0.86 to -1.67 kg) exceeding those observed with placebo (-0.28 kg, p = 0.019 for 200 mg RO-151 vs. placebo). Insulin sensitivity parameters (e.g. HOMA-IR and Matsuda-Index) improved non-significantly with 200 mg RO-151. Lipid parameters did not consistently improve with ...

Journal of medical microbiology, 2000

Three Shiga toxin (Stx)-producing Escherichia coli (STEC) strains from patients with diarrhoea we... more Three Shiga toxin (Stx)-producing Escherichia coli (STEC) strains from patients with diarrhoea were identified, each of which contained three distinct stx genes (stx1, stx2 and stx2c). The strains belonged to the serotypes O52:H19, O75:H- and O157:H- and harboured eae and EHEC-hly sequences. Colony-blot immunoassay was used to demonstrate that both major types of Stx were expressed. The association of stx genes with either phage or phage DNA was demonstrated in all three strains. Isolated phage DNA from all strains contained stx1 sequences, but stx2 sequences were found only in phage DNA of two of these strains. The presence of three distinct stx genes may enhance the virulence of STEC strains and should be monitored. The observations demonstrate not only the potential of stx genes to spread within different serotypes, but also their capacity to accumulate within a single strain.

Guide to Paediatric Drug Development and Clinical Research, 2010

The lancet. Diabetes & endocrinology, 2014

The prevalence of non-alcoholic fatty liver disease is increasing worldwide and an effective and ... more The prevalence of non-alcoholic fatty liver disease is increasing worldwide and an effective and safe pharmacological treatment is needed. We investigated whether inhibition of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1, also known as HSD11B1) by RO5093151 could safely and effectively decrease liver-fat content in patients with this disorder. We did this phase 1b trial at four centres in Germany and Austria. Participants with non-alcoholic fatty liver disease (defined as (1)H magnetic resonance spectroscopy liver-fat content >5·56%), insulin resistance (homoeostatic model assessment of insulin resistance [HOMA-IR] of at least 2·0 mmol/L·mU/L), BMI greater than 27 kg/m(2), and aged 35-65 years were randomly assigned by interactive voice response system in a 1:1 ratio, stratified for triglyceride concentration (<1·7 mmol/L or ≥1·7 mmol/L), to oral RO5093151 (200 mg twice daily) or matching placebo for 12 weeks. The main exclusion criteria were other liver diseases, aspart...

Journal of Pediatric Endocrinology and Metabolism, 2000

Vocal disturbances in women with congenital adrenal hyperplasia and androgen excess should be ext... more Vocal disturbances in women with congenital adrenal hyperplasia and androgen excess should be extremely rare today since effective substitution with glucocorticoids is available. We present a 17 year-old female with congenital adrenal hyperplasia due to 21-hydroxylase deficiency and severe virilization because of long-term insufficient therapy. Laboratory data showed elevated serum levels of testosterone, 17-hydroxyprogesterone, plasma ACTH and a high excretion of urinary pregnanetriol. The phoniatric aspect showed a masculine voice. We discuss the different effects of androgens on the pubertal larynx and various hormonal disturbances that may cause voice changes as well as therapeutic options of voice therapy. From the pediatric point of view it might be important to perform a phoniatric examination in girls with congenital adrenal hyperplasia during puberty in order to monitor androgen effects.

The Journal of Clinical Pharmacology, 2012

This article aims to provide an overview of the current situation regarding pharmacogenetic and p... more This article aims to provide an overview of the current situation regarding pharmacogenetic and pharmacogenomic (PG) studies in pediatrics, with a special focus on the role of PG data in the regulatory decision-making process. Despite the gap in pharmacogenetic research due to the lack of translational studies in adults and children, several technologies exist in drug development and biomarkers validation, which could supply valuable information concerning labeling and dosing recommendations. If performed under strict good clinical practice quality criteria, such findings could be included in the submission package of new chemical entities and used as additional information for prescribers, supporting further evaluation and understanding of the efficacy and safety profile of new medicines. Even though regulatory authorities may be aware of the potential role of PG in medical practice and guidances are available about the integration of PG in drug development, most data obtained from PG studies are not used by prescribers. The challenge is to better understand whether PG markers can be used to assess potential differences in drug response during the clinical program, so PG data can be integrated into the regulatory decision-making process, enabling the introduction of labeling information that promotes optimal dosing in the pediatric population.

Diabetes, Obesity and Metabolism, 2008

To compare the end-organ metabolic effects of insulin glulisine (glulisine), insulin lispro (lisp... more To compare the end-organ metabolic effects of insulin glulisine (glulisine), insulin lispro (lispro) and regular human insulin (RHI) in patients with type 1 diabetes mellitus. Methods: Eighteen patients with type 1 diabetes mellitus (mean age 36.9 AE 8.6 years, BMI 23.6 AE 2.8 kg/m 2 , haemoglobin A 1c 7.4 AE 0.9%) were randomized in this single-centre, double-blind, three-period cross-over, standard Latin-square, euglycaemic glucose clamp trial. Patients received sequential, primed stepwise intravenous infusions of glulisine, lispro or RHI (infusion rates were increased in a stepwise manner from an initial rate of 0.33 [180 min] to 0.66 [180 min] and 1.00 [180 min] mU/kg/min). The primary variables were the suppression of endogenous glucose production (S EGP ) and glucose uptake (GU). Results: Mean basal endogenous glucose production (EGP) was 1.88, 2.12 and 2.12 mg/kg/min for glulisine, lispro and RHI respectively. Mean (AEs.e.) maximum absolute S EGP (adjusted for basal EGP) was À1.64 AE 0.06, À1.72 AE 0.05 and À1.56 AE 0.05 mg/kg/min respectively. Mean (AEs.e.) maximum absolute increase in GU (adjusted for basal GU) was 6.46 AE 0.26, 6.23 AE 0.24 and 6.72 AE 0.24 mg/kg/min respectively. There were no clinically relevant differences between the three insulin treatments with respect to serum insulin, free fatty acid (FFA), glycerol or lactate levels. No serious adverse events and no episodes of severe hypoglycaemia were reported. Conclusions: This study shows that glulisine, lispro and RHI have similar effects on S EGP , GU, FFA, glycerol and lactate levels, providing evidence for similar end-organ metabolic effects.