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Biomedical subjects

A Dressler

Publications and source records attributed to A Dressler.

10 recordsLinked to original sources

A one-year, randomised, multicentre trial comparing insulin glargine with NPH insulin in combination with oral agents in patients with type 2 diabetes.

AIMS: The aim of the trial was to compare the efficacy and safety of the new, long-acting basal insulin, insulin glargine (LANTUS(R)), with NPH human insulin, each administered in a combination regimen with oral antidiabetic drugs in patients with Type 2 diabetes. METHODS: In a multicentre, open, randomised study, 570 patients with Type 2 diabetes, aged 34 - 80 years, were treated for 52 weeks with insulin glargine or NPH insulin given once daily at bedtime. Previous oral antidiabetic therapy was continued throughout the study. RESULTS: There was a clinically relevant decrease in glycosylated haemoglobin (GHb) values from baseline to endpoint with both drugs (insulin glargine: - 0.46 %; NPH insulin: - 0.38 %; p = 0.415); also, this difference was statistically significant in the subgroup of overweight patients with BMI > 28 kg/m 2 (insulin glargine: - 0.42 %, NPH insulin: - 0.11 %; p = 0.0237). Over the entire treatment period, NPH insulin-treated patients (41 %) and insulin glargine-treated patients (35 %) experienced a similar level of symptomatic hypoglycaemia. A statistically significant difference was observed in the number of patients treated with NPH insulin who reported at least one episode of nocturnal hypoglycaemia compared with those treated with insulin glargine in the overall population and in the overweight subgroup (overall: 24 % vs. 12 %, p = 0.002; overweight: 22.2 % vs. 9.5 %, p = 0.0006), using the Cochran-Mantel-Haenszel test. These differences were most pronounced in insulin-naïve and overweight (BMI > 28 kg/m 2) sub-groups. The incidence of adverse events was similar for the two treatments. CONCLUSIONS: This study demonstrated that insulin glargine is as effective as NPH insulin in achieving glycaemic control in patients with Type 2 diabetes, and is associated with fewer episodes of symptomatic hypoglycaemia, particularly nocturnal episodes.

Adult↗

No evidence for accumulation of insulin glargine (LANTUS): a multiple injection study in patients with Type 1 diabetes.

AIMS: Insulin glargine is a long-acting insulin analogue that is metabolically active for at least 24 h. We investigated the multiple-dose pharmacokinetic properties of insulin glargine to determine whether daily injections lead to the accumulation of circulating insulin levels and a corresponding decrease in blood glucose levels in patients with Type 1 diabetes. METHODS: Fifteen patients using preprandial insulin lispro (mean age 36 +/- 9 years, body mass index 24.6 +/- 2.2 kg/m(2)) completed the study. Each patient's optimal insulin glargine dose was determined during a dose-finding phase. After a washout period, patients were treated over 12 days with a constant daily dose of insulin glargine injected in the abdominal subcutaneous adipose tissue at 22:00 h, and with preprandial insulin lispro. Free serum insulin (FSI) and blood glucose concentrations were assessed hourly after the first, fourth, and eleventh injection, after which patients fasted for 24 h and did not use any other insulin preparation. RESULTS: There were no changes in daily insulin doses during the dose-finding phase (insulin glargine: initial dose 24 +/- 6 IU, mean change 0 +/- 3 IU; insulin lispro: 18 +/- 9 IU, 0 +/- 7 IU). The time course of FSI was comparable on the three pharmacokinetic study days. Notably, the trough FSI at the end of the sampling periods was almost identical (day 1, 79 +/- 56 pmol/l, day 4, 77 +/- 56 pmol/l, day 11, 86 +/- 60 pmol/l). No changes occurred in any of the pharmacokinetic parameters studied. CONCLUSIONS: There is no evidence that insulin glargine accumulates after multiple injections over 12 days. These results indicate that the predetermined dose of insulin glargine will not need to be reduced after commencing treatment because of a risk of accumulation.

C-Peptide↗

The early markers for later dyskinetic cerebral palsy are different from those for spastic cerebral palsy.

Qualitative abnormalities of spontaneous motor activity in newborns and young infants are early predictive markers for later spastic cerebral palsy. Aim of this research was to identify which motor patterns may be specific for later dyskinetic cerebral palsy. In a large, prospectively performed longitudinal study involving four European hospitals we identified twelve cases with the relatively rare condition of dyskinetic cerebral palsy and compared their early motor development with twelve spastic cerebral palsy cases and twelve controls. From birth to the fifth month post-term, all infants were repeatedly videoed and their spontaneous motor patterns, including general movements, were assessed. Until the second month post-term, the infants that later became dyskinetic displayed a poor repertoire of general movements, "arm movements in circles" and finger spreading. Abnormal arm and finger movements remained until at least five months and were then concurrent with a lack of arm and leg movements towards the midline. Later dyskinetic infants share with later spastic infants the absence of fidgety movements, a spontaneous movement pattern that is normally present from three to five months. Qualitative assessment of spontaneous motor patterns enabled us to identify infants at high risk for dyskinetic cerebral palsy early in life. Additionally, we were able to discriminate them from those infants at high risk for later spastic cerebral palsy. This is a matter of significant clinical relevance because the two types of cerebral palsy ask for different management and early intervention.

Biomarkers↗

Less nocturnal hypoglycemia and better post-dinner glucose control with bedtime insulin glargine compared with bedtime NPH insulin during insulin combination therapy in type 2 diabetes. HOE 901/3002 Study Group.

OBJECTIVE: Available basal insulin formulations do not provide a constant and reliable 24-h insulin supply. We compared the efficacy and safety of glargine (a long-acting insulin analog) and NPH insulins in insulin-naive type 2 diabetic patients treated with oral antidiabetic agents. RESEARCH DESIGN AND METHODS: There were 426 type 2 diabetic patients (age 59 +/- 9 years, BMI 28.9 +/- 4.3 kg/m2, mean +/- SD) with poor glycemic control on oral antidiabetic agents randomized to treatment for 1 year with bedtime insulin glargine or bedtime NPH insulin. Oral agents were continued unchanged. The fasting blood glucose (FBG) target was 6.7 mmol/l (120 mg/dl). RESULTS: Average glycemic control improved similarly with both insulins (HbA(1c), [reference range <6.5%] 8.3 +/- 0.1 vs. 8.2 +/- 0.1% at 1 year, glargine vs. NPH, mean +/- SEM, P < 0.001 vs. baseline for both). However, there was less nocturnal hypoglycemia (9.9 vs. 24.0% of all patients, glargine vs. NPH, P < 0.001) and lower post-dinner glucose concentrations (9.9 +/- 0.2 vs. 10.7 +/- 0.3 mmol/l, P < 0.02) with insulin glargine than with NPH. Insulin doses and weight gain were comparable. In patients reaching target FBG, HbA(1c) averaged 7.7 and 7.6% in the glargine and NPH groups at 1 year. CONCLUSIONS: Use of insulin glargine compared with NPH is associated with less nocturnal hypoglycemia and lower post-dinner glucose levels. These data are consistent with peakless and longer duration of action of insulin glargine compared with NPH. Achievement of acceptable average glucose control requires titration of the insulin dose to an FBG target < or =6.7 mmol/l. These data support use of insulin glargine instead of NPH in insulin combination regimens in type 2 diabetes.

Adult↗

A First Comparison of the Surface Brightness Fluctuation Survey Distances with the Galaxy Density Field: Implications for H0 and Omega.

We compare the peculiar velocities measured in the surface brightness fluctuation survey of galaxy distances with the predictions from the density fields of the IRAS 1.2 Jy flux-limited redshift survey and the optical redshift survey (ORS) to derive simultaneous constraints on the Hubble constant H0 and the density parameter beta=Omega0.6&solm0;b, where b is the linear bias. We find that betaI=0.42+0.10-0.06 and betaO=0.26+/-0.08 for the IRAS and ORS comparisons, respectively, and that H0=74+/-4 km s-1 Mpc (with an additional 9% uncertainty due to the Cepheids themselves). The match between predicted and observed peculiar velocities is good for these values of H0 and beta, and although there is covariance between the two parameters, our results clearly point toward low-density cosmologies. Thus, the unresolved discrepancy between the "velocity-velocity" and "density-density" measurements of beta continues.

Journal Article↗

Cytogenetic alterations in eight mammary tumors and tumor-suppressor gene p53 mutation in one mammary tumor from dogs.

OBJECTIVE: To identify mutations in canine mammary tumors. ANIMALS: 10 tumor-bearing dogs. PROCEDURE: Culture of neoplastic cells originating from mammary tumors was performed, and trypsin-G banding was used for cytogenetic investigations. The same tumors were subjected to molecular genetic screening by use of DNA extraction, polymerase chain reaction, DNA elution, and DNA sequencing for ras oncogenes and the p53 tumor suppressor gene. RESULTS: A broad spectrum of chromosome aberrations was observed, including trisomies, reciprocal translocations, and structural and numerical X-chromosome alterations and deletions. Molecular genetic analysis revealed a tumor suppressor p53 gene mutation in codon 249 of exon 7 in one instance. Interestingly, analyzed mammary tumors were free of mutations in N-ras, K-ras and H-ras, exons 1 and 2. CONCLUSIONS: Chromosome alterations are wide-spread in canine mammary tumors, but no ras family mutations were detected in tumors from these 10 dogs. CLINICAL RELEVANCE: Knowledge about chromosome, oncogene, and tumor suppressor gene damage could be helpful for diagnosis and prognosis of neoplastic diseases in dogs.

Adenocarcinoma↗

A randomized multicentre trial of insulin glargine compared with NPH insulin in people with type 1 diabetes.

BACKGROUND: To compare insulin glargine with NPH human insulin for basal insulin supply in adults with type 1 diabetes. METHODS: People with type 1 diabetes (n = 585), aged 17-77 years, were randomized to insulin glargine once daily at bedtime or NPH insulin either once- (at bedtime) or twice-daily (in the morning and at bedtime) according to their prior treatment regimen and followed for 28 weeks in an open-label, multicentre study. Both groups continued with pre-meal unmodified human insulin. RESULTS: There was no significant difference between the two insulins in change in glycated haemoglobin from baseline to endpoint (insulin glargine 0.21 +/- 0.05% (mean +/- standard error), NPH insulin 0.10 +/- 0.05%). At endpoint, self-monitored fasting blood glucose (FBG) had decreased similarly in each group (insulin glargine -1.17 +/- 0.12 mmol/L, NPH insulin -0.89 +/- 0.12 mmol/L; p = 0.07). However, people on >1 basal insulin injection per day prior to the study had a clinically relevant decrease in FBG on insulin glargine versus NPH insulin (insulin glargine -1.38 +/- 0.15 mmol/L, NPH insulin -0.72 +/- 0.15 mmol/L; p < 0.01). No significant differences in the number of people reporting >or=1 hypoglycaemic episode were found between the two groups, including severe and nocturnal hypoglycaemia. Insulin glargine was well tolerated, with a similar rate of local injection and systemic adverse events versus NPH insulin. CONCLUSIONS: A single, bedtime, subcutaneous dose of insulin glargine provided a level of glycaemic control at least as effective as NPH insulin, without an increased risk of hypoglycaemia.

Adolescent↗