Biomedical subjects

W Brannath

Publications and source records attributed to W Brannath.

8 recordsLinked to original sources

PubMed2005

Optical coherence tomography guided retreatment of photodynamic therapy.

AIM: To evaluate the results of a retreatment modality of photodynamic therapy (PDT) based on optical coherence tomography (OCT) and fluorescein angiography (FA). To quantify the effect of PDT with the help of measurement of the retinal thickness. METHODS: Eyes with predominantly classic subfoveal choroidal neovascularisation (CNV) due to age related macular degeneration were included. PDT was performed every three months, when needed. OCT, FA, and measures of distance acuity were performed at baseline, after 6 weeks, 3 months, and from then on every 3 months. A control group of a consecutive series of eyes that had been retreated based only on FA results was installed. RESULTS: Forty eyes of 38 patients were included. The average age was 73 years. The maximum retinal thickness decreased from 404 mum at baseline to 281.6 mum at month 12. Furthermore there was a significant decrease of retinal thickness in both subgroups. The number of retreatments was reduced, when activity was diagnosed using OCT and FA. (2.4 v 4.0). The distance acuity correlated significantly with the maximum retinal thickness (p=0.0042). CONCLUSION: Information about the activity of a neovascular lesion can be obtained with the help of OCT. The retreatment modalities can be optimised by using OCT and FA and the number of retreatments can be reduced.

Aged↗

PubMed2003

Sequential tests for noninferiority and superiority.

The problem of simultaneous sequential tests for noninferiority and superiority of a treatment, as compared to an active control, is considered in terms of continuous hierarchical families of one-sided null hypotheses, in the framework of group sequential and adaptive two-stage designs. The crucial point is that the decision boundaries for the individual null hypotheses may vary over the parameter space. This allows one to construct designs where, e.g., a rigid stopping criterion is chosen, rejecting or accepting all individual null hypotheses simultaneously. Another possibility is to use monitoring type stopping boundaries, which leave some flexibility to the experimenter: he can decide, at the interim analysis, whether he is satisfied with the noninferiority margin achieved at this stage, or wants to go for more at the second stage. In the case where he proceeds to the second stage, he may perform midtrial design modifications (e.g., reassess the sample size). The proposed approach allows one to "spend," e.g., less of alpha for an early proof of noninferiority than for an early proof of superiority, and is illustrated by typical examples.

Humans↗

PubMed2001

As to the clastogenic-, sister-chromatid exchange inducing-and cytotoxic activity of inosine triphosphate in cultures of human peripheral lymphocytes.

The influence of commercial inosine triphosphate (ITP) on the chromosome aberration rate, the mitotic rate, sister-chromatid exchange (SCE) frequency, and the proportion of first (X1), second (X2) and third (X3) division metaphases was investigated in 72h cultures of human peripheral lymphocytes. The blood donors had mild inactive arthrosis and a normal health check-up. All cultures of each volunteer were set-up simultaneously. In contrast to a previous report [Arch. Biochem. Biophys. 278 (1990) 238-244], it was demonstrated in two preliminary studies (number of subjects, n=5 each) that ITP at a final concentration of 100 microM does not induce chromosomal aberrations and, furthermore, that not ITP concentrations higher than 100 microM but ITP doses higher than 3.8mM prohibit culture growth. Based on these results, cultures with a final ITP concentration of 3.6mM (max.) and 1.8mM (max./2) were compared with control cultures (number of subjects n=10; three males and seven females, mean age x=57.6 years). Whereas no increase in the chromosomal breakage rate was observed in cultures with an ITP concentration of 1.8mM and only a marginally significant one (P=0.048) for 3.6mM ITP cultures, a highly significant induction of SCEs, not only at an ITP concentration of 3.6mM (P<0.0001) but also at 1.8mM (P<0.0001) was seen. The increase in the SCE frequency was not linear, but steeper from 0 to 1.8mM than from 1.8 to 3.6mM. Nevertheless, the difference between 1.8 and 3.6mM cultures was significant (P=0.027). The distribution of the number of SCEs per metaphase as well as the distribution of SCEs per chromosome correspond to the expected Poisson values. The investigation of the cytotoxic effect of the studied ITP concentrations revealed a highly significant reduction of the mitotic rate from 0 to 1.8mM as well as from 1.8 to 3.6mM in the aberration studies (all P values are equal to smallest possible one for a sample size of 10, namely, 0.002), and in the SCE studies there is a significant decrease in the X3 frequency when ITP is increased (0-1.8mM: P=0.0061 and 1.8-3.6mM: P<0.0001). The proportion of X1 within all X1 and X2 metaphases changes significantly only at the second dose step (0-1.8mM ITP: P=0.22 and 1.8-3.6mM ITP: P<0.0001). The results are discussed.

Cell Division↗

PubMed2001

A cream containing the chelator DTPA (diethylenetriaminepenta-acetic acid) can prevent contact allergic reactions to metals.

Chelating agents in protective barrier creams have often been used in the prevention of allergic contact dermatitis to nickel. In a pilot study, we demonstrated the preventive effect of 10% diethylenetriaminepentaacetic acid (DTPA) in an oil-in-water emulsion in nickel-sensitized patients. Now we reproduced these results in a randomized, double-blind study. Additionally, we investigated the efficacy of the barrier cream in other clinically relevant metal allergies. Individuals sensitized to various metals had a significant decrease in positive patch test reactions after pre-treatment with the DTPA-cream: 2.5% nickel sulfate (24/28 positive without pre-treatment versus 1/28 with pre-treatment; p<0.0001), 5% nickel sulfate (30/32 versus 15/32; p=0.0003), 1% cobalt chloride (19/20 versus 6/20; p=0.001) and 5% copper sulfate (13/14 versus 5/14; p=0.02). However, the cream had no protective effect with 1% palladium chloride (17/23 versus 16/23) and with 0.5% potassium dichromate (9/13 versus 7/13). We conclude that the DTPA-cream clearly abrogates positive patch test reactions in nickel-, cobalt- and copper-sensitized subjects and that it may therefore be helpful in the management of allergic contact dermatitis.

Chelating Agents↗

PubMed2001

The effect of remifentanil on the heat pain threshold in volunteers.

Remifentanil offers a wide range of clinical uses and has been successfully combined with general anesthetics. However, there are few human experimental studies demonstrating the analgesic property of remifentanil. It was our aim to determine the analgesic effect of remifentanil with regard to dose-dependent increments in a human model of heat pain threshold assessment. Twenty healthy volunteers were randomized in a double-blinded cross-over design to receive an infusion of remifentanil or saline. The stepped infusion was increased every 5 min by 0.01 microg. kg(-1). min(-1) up to 0.17 microg. kg(-1). min(-1)and terminated in case of defined safety limits. Thermal sensory testing of the heat pain threshold was performed every 5 min at the left forearm. The dose-response relationship and the effective dose for at least 50% of the subjects (ED(50)) were determined. Remifentanil led to a clear dose-dependent increase of the heat pain threshold differing significantly from placebo (P < 0.0007). The ED(50) of remifentanil equals 0.05 microg. kg(-1). min(-1) (first quartile 0.025 microg. kg(-1). min(-1) and third quartile 0.06 microg. kg(-1). min(-1)) in this experimental setting. In conclusion, an opioid-mediated analgesic effect of remifentanil was determined in a human heat pain threshold model. The dose of 0.05 microg. kg(-1). min(-1) is an effective and safe increment in healthy volunteers.

Adult↗

PubMed2001

Flexible two-stage designs: an overview.

In this overview we introduce the basic ideas behind a new flexible approach in sequential designs. The different concepts based on two-stage combination tests and conditional error functions are brought together. We sketch the construction of p-values, confidence intervals, and median unbiased estimates. Finally, recursive combination tests are introduced which extend the flexibility to the choice of the number of interim analyses.

Clinical Trials as Topic↗

PubMed2000

Bronchoplastic procedures in malignant and nonmalignant disease: multivariable analysis of 144 cases.

OBJECTIVES: We sought to analyze the experience with bronchoplastic procedures over a 7-year period and to determine putative prognostic factors for survival. METHODS: From 1991 to 1997, 144 bronchoplastic procedures were performed for non-small cell lung cancer (n = 123), small cell lung cancer (n = 5), carcinoid tumor (n = 10), and metastases of extrathoracic malignant tumors (n = 6). There were 111 sleeve lobectomies, 17 bilobectomies, 4 lobectomies with carinal resection, 8 sleeve pneumonectomies, and 4 bronchotomies without parenchymal resection. Multivariable analysis included risk factors, such as age, sex, type of bronchoplastic procedure (bronchotomy, lobectomy, bilobectomy, or pneumonectomy), additional angioplasty, TNM staging, histology, radicality of resection, respiratory risk (forced expiratory volume in 1 second, percent predicted < 60), cardiovascular risk, and adjuvant therapy. RESULTS: Overall 1- and 3-year survival was 72% and 52%, respectively. The overall 30-day mortality was 8.3% (5.4% for single sleeve lobectomies). Multivariable analysis demonstrated 4 risk factors for survival. High tumor stage, type of bronchoplastic procedure, impaired lung function, and presence of cardiovascular risk were associated with a poor outcome. Univariate analysis showed reduced survival in patients with sleeve pneumonectomies (1-year survival, 25%). CONCLUSIONS: Bronchoplastic procedures for central tumors and sleeve pneumonectomies are associated with poor survival. Careful selection of these patients, as well as of patients with impaired lung function and cardiovascular risk factors, is mandatory.

Adult↗

PubMed1999

Gastric emptying in Type II (non-insulin-dependent) diabetes mellitus before and after therapy readjustment: no influence of actual blood glucose concentration.

AIMS/HYPOTHESIS: Hyperglycaemia that is induced short-term slows gastric emptying in healthy subjects and patients with diabetes mellitus. Little information is available on the impact of longer-lasting, naturally occurring blood glucose increases and their reduction to euglycaemic values. We studied the relation between gastric emptying and pre-prandial and postprandial blood glucose concentrations in patients with Type II (non-insulin-dependent) diabetes mellitus and secondary failure to respond to oral hypoglycaemic treatment (a) before readjusting hypoglycaemic therapy and (b) 1 week thereafter. METHODS: We studied 9 female and 1 male patient (age 60-78 years, BMI 21.9-32.5 kg/m2, diabetes duration 3-33 years, HbA1c 8.8-13.2%). Gastric emptying of a radiolabelled semisolid 1168 kJ meal was recorded scintigraphically. RESULTS: Blood glucose concentration pre-prandial and postprandial was considerably lower subsequent to than before therapy readjustment in all patients (fasting, 7.9 mmol/l+/-1.5 SD vs 11.7+/-1.7 mmol/l; 60 min postprandial, 11.7+/-2.0 vs 15.4+/-2.2 mmol/l). By contrast, gastric emptying was unchanged (residual radioactivity in stomach 50 min postprandial 65.7+/-14.1% vs 66.5+/-12.9%). There was no relation between emptying and either fasting blood glucose concentration or its postprandial increase. CONCLUSION/INTERPRETATION: The data do not support a major impact of actual, longer-lasting, naturally occurring blood glucose concentrations upon the rate of gastric emptying in patients with Type II diabetes.

Adult↗