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Biomedical subjects

D Ziegler

Publications and source records attributed to D Ziegler.

At least 19 recordsLinked to original sources
PubMed2006

Altered cerebral regulation in type 2 diabetic patients with cardiac autonomic neuropathy.

AIMS/HYPOTHESIS: Assessment of cerebral regulation in diabetic patients is often problematic because of the presence of cardiac autonomic neuropathy. We evaluated the technique of oscillatory neck suction at 0.1 Hz to quantify cerebral regulation in diabetic patients and healthy control subjects. SUBJECTS AND METHODS: In nine type 2 diabetic patients with cardiac autonomic neuropathy and 11 age-matched controls, we measured blood pressure and cerebral blood flow velocity responses to application of 0.1 Hz neck suction. We determined spectral powers and calculated the transfer function gain and phase shift between 0.1 Hz blood pressure and cerebral blood flow velocity oscillations as parameters of cerebral regulation. RESULTS: In the patients and control subjects, neck suction did not significantly influence mean values of the RR interval, blood pressure and cerebral blood flow velocity. The powers of 0.1 Hz blood pressure and cerebral blood flow velocity oscillations increased in the control subjects, but remained stable in the patients. Transfer function gain remained stable in both groups. Phase shift decreased in the patients, but remained stable in control subjects. CONCLUSIONS/INTERPRETATION: The absence of an increase in the power of 0.1 Hz blood pressure and cerebral blood flow velocity oscillations confirmed autonomic neuropathy in the diabetic patients. Gain analysis did not show altered cerebral regulation. The decrease in phase shift in the patients indicates a more passive transmission of neck suction-induced blood pressure fluctuations onto the cerebrovascular circulation, i.e. altered cerebral regulation, in the patients, and is therefore suited to identifying subtle impairment of cerebral regulation in these patients.

Autonomic Nervous System Diseases↗
PubMed2006

Interferometric coupling of the Keck telescopes with single-mode fibers.

Here we report successful interferometric coupling of two large telescopes with single-mode fibers. Interference fringes were obtained in the 2- to 2.3-micrometer wavelength range on the star 107 Herculis by using the two Keck 10-meter telescopes, each feeding their common interferometric focus with 300 meters of single-mode fibers. This experiment demonstrates the potential of fibers for future kilometric arrays of telescopes and is the first step toward the 'OHANA (Optical Hawaiian Array for Nanoradian Astronomy) interferometer at the Mauna Kea observatory in Hawaii. It opens the way to sensitive optical imagers with resolutions below 1 milli-arc second. Our experimental setup can be directly extended to large telescopes separated by many hundreds of meters.

Journal Article↗
PubMed2006

Selective contribution of diabetes and other cardiovascular risk factors to cardiac autonomic dysfunction in the general population.

Both cardiac autonomic dysfunction adn cardiovascular risk factors are related to and excess risk of mortality. We sought to determine whether the major cardiovascular risk factors are associated with diminished heart rate variability (HRV), prolonged QTc interval, or increased QT dispersion (QTD). Male (n = 1030) and female (n = 957) subjects, aged 55-74 years, who participated in the population-based MONICA Augsburg survey 1989/90 were assessed for the presence of cardiovascular risk factors such as diabetes, hypertension, obesity, dyslipidemia, smoking, and low physical activity. Lowest quartiles for time domain indexes of HRV (SD of R-R intervals [SDNN], max-min difference), QTc > 440 ms, and QTD > 60 ms determined from 12-lead resting ECG were used as cutpoints. In men, after adjustment for age and alcohol consumption, significant independent determinants for the lowest quartiles of SDNN were diabetes, obesity, and smoking. Independent contributors to prolonged QTc were hypertension, obesity, smoking, and low physical activity, whereas for increased QTD it was only hypertension. In women, diabetes was the only contributor to low SDNN, and hypertension was the only determinant of prolonged QTc. In conclusion, diabetes is the primary determinant of reduced HRV in the general population, while hypertension is the primary contributor to prolonged QTc in both sexes. However, obesity and smoking contribute to autonomic dysfunction in men but not women. Thus, a selectivity and sex-related differences exist among the various cardiovascular risk factors as to their influence on autonomic dysfunction.

Aged↗
PubMed2006

[Duloxetine, a new therapeutic option for diabetic peripheral neuropathic pain].

Diabetics develop numerous chronic associated diseases, among them sensory polyneuropathy. Diabetic polyneuropathy (DPN) often causes pain of various kinds, degree and duration. There are many pharmacological approaches: antidepressants are also important. Duloxetine is a recently approved dual action serotonin and noradrenaline re-uptake inhibitor that in its analgesic efficacy is comparable to established drugs. Duloxetine, in a dosage of 60 mg x 1 or x 2 daily, significantly reduces, from the first week of administration, the pain of DPN, when compared with a placebo. The most commonly observed side effects have been nausea, sleepiness, constipation and fatigue. On average duloxetine has not shown any clinically relevant increase in blood pressure, pulse rate and weight. It thus offers a new option as part of the treatment of pain caused by DPN. The various drugs should be considered individually in any treatment algorithm, also taking into account their side effects. Psychotherapeutic methods serve to support the overcoming of pain.

Adrenergic Uptake Inhibitors↗
PubMed2005

Urinary 8-epi-PGF2alpha and its endogenous beta-oxidation products (2,3-dinor and 2,3-dinor-5,6-dihydro) as biomarkers of total body oxidative stress.

Although measurements of plasma F2-isoprostanes are established markers of oxidative stress, their quantification only reflects acute non-enzymatic lipid peroxidation. In this study, a new approach is described for the rapid isolation and measurement of urinary 8-epi-PGF2alpha and its endogenous beta-oxidation metabolites (2,3-dinor-8-epi-PGF2alpha and 2,3-dinor-5,6-dihydro-PGF2alpha) for use as index of total body oxidative stress. Isoprostanes were partitioned with ethyl acetate and subsequently purified by chromatography on an aminopropyl (NH2) and silica (Si) cartridge. Final analysis of F2-isoprostanes as trimethylsilyl-ester/pentafluorobenzyl ester derivatives was carried out by stable isotope dilution mass spectrometry. Overall recovery of F2-isoprostanes was 80+/-4%. Inter- and intra-assay coefficients of variation were 5% and 7%, respectively. In a group of healthy humans, the mean excretion rates expressed as nmol/mmol creatinine for 2,3-dinor-8-epi-PGF2alpha, 2,3-dinor-5,6-dihydro-8-epi-PGF2alpha, and 8-epi-PGF2alpha were 5.43+/-1.93, 2.16+/-0.71, and 0.36+/-0.16, respectively. Correlations were obtained between 8-epi-PGF2alpha and 2,3-dinor-8-epi-PGF2alpha or 2,3-dinor-5,6-dihydro-8-epi-PGF2alpha (r=0.998 and r=0.937, respectively). A strong relationship was also seen between 2,3-dinor-8-epi-PGF2 and 2,3-dinor-5,6-dihydro-8-epi-PGF2alpha (r=0.949). The new technique allows for high sample throughput and avoids the need for HPLC and/or other expensive equipment required for the initial sample preparation. Simultaneous analysis of urinary 8-epi-PGF2alpha and its metabolites should provide unique tool in clinical trials exploring the role of oxidant injury in human disease.

Adult↗
PubMed2005

Effective treatment of symptomatic diabetic polyneuropathy by high-frequency external muscle stimulation.

AIMS/HYPOTHESIS: Diabetic distal symmetrical sensory polyneuropathy (DSP) affects 20-30% of diabetic patients. Transcutaneous electrical nerve stimulation (TENS) and electrical spinal cord stimulation have been proposed as physical therapies. We performed a controlled, randomised pilot trial to compare the effects of high-frequency external muscle stimulation (HF) with those of TENS in patients with symptomatic DSP. METHODS: Patients with type 2 diabetes and DSP (n=41) were randomised to receive treatment with TENS or HF using strata for non-painful (n=20) and painful sensory symptoms (n=21). Both lower extremities were treated for 30 min daily for three consecutive days. The patients' degree of symptoms and pain were graded daily on a scale of one to ten, before, during and 2 days after treatment termination. Responders were defined by the alleviation of one or more symptoms by at least three points. RESULTS: The two treatment groups were similar in terms of baseline characteristics, such as age, duration of diabetes, neurological symptoms scores and neurological disability scores. The responder rate was significantly higher (p<0.05) in the HF group (80%, 16 out of 20) than in the TENS group (33%, seven out of 21). Subgroup analysis revealed that HF was more effective than TENS in relieving the symptoms of non-painful neuropathy (HF: 100%, seven out of seven; TENS: 44%, four out of nine; p<0.05) and painful neuropathy (HF: 69%, nine out of 13; TENS: 25%, three out of 12; p<0.05). The responders did not differ in terms of the reduction in mean symptom intensity during the trial. CONCLUSIONS/INTERPRETATION: This pilot study shows, for the first time, that HF can ameliorate the discomfort and pain associated with DSP, and suggests that HF is more effective than TENS. External muscle stimulation offers a new therapeutic option for DSP.

Adult↗
PubMed2005

Parylene flexible neural probes integrated with microfluidic channels.

The fluidic channel in the flexible probe has three functions: (i) to inject chemicals into the tissues, (ii) to measure the neural activities from the tissues, and (iii) to improve the mechanical stiffness of the probe by filling the channel with a solid material. A 10-microm-thick microfluidic channel was embedded into the probe by using sacrificial photoresist patterns. Polyethylene glycol (PEG), which is solid at room temperature and dissolves when in contact with water, was used to fill the channel and increase the stiffness of the probe before insertion into the tissue. The impedance of the electrode inside the fluidic channel was around 100 kOmega at 1 kHz when the channel was filled with saline solution. We were able to insert the probe into a rat's brain and measure the neural signals with the electrode.

Animals↗
PubMed2005

Type 2 diabetes as an inflammatory cardiovascular disorder.

Type 2 diabetes carries a 2-6-fold increased risk of cardiovascular disease (CVD) and death. Indeed, the risk of major cardiovascular events in Type 2 diabetic patients without history of coronary heart disease (CHD) is equivalent to that observed in non-diabetic subjects with CHD. However, atherosclerosis may also precede the development of diabetes, suggesting that both disorders share common genetic and environmental antecedent factors ("common soil" hypothesis). One such a possible ancestor is insulin resistance which constitutes both a major feature of Type 2 diabetes and an independent risk factor for CHD. It is well documented that inflammatory processes play an important role in the causation of atherosclerotic CVD. Inflammatory mediators play a paramount role in the initiation, progression, and rupture of atherosclerotic plaques. Thus, markers of inflammation and endothelial dysfunction may provide additional information about a patient's risk of developing CVD and may become new targets for treatment. On the other hand, evidence has emerged suggesting that inflammation is also involved in the development of Type 2 diabetes. Prospective studies have demonstrated that increased levels of pro-inflammatory markers such as CRP or reduced levels of anti-inflammatory markers such as adiponectin predict the development of Type 2 diabetes. Thus, there is accumulating evidence suggesting that inflammation is the bridging link between atherosclerosis and the metabolic syndrome. Interventions by lifestyle modification or agents with anti-inflammatory properties may reduce the risk of both conditions. Drugs exerting anti-inflammatory and vascular effects have future potential to be used within an array of interventions aimed at reducing the enormous cardiovascular burden associated with Type 2 diabetes.

Adiponectin↗
PubMed2004

Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a meta-analysis.

AIMS: To determine the efficacy and safety of 600 mg of alpha-lipoic acid given intravenously over 3 weeks in diabetic patients with symptomatic polyneuropathy. METHODS: We searched the database of VIATRIS GmbH, Frankfurt, Germany, for clinical trials of alpha-lipoic acid according to the following prerequisites: randomized, double-masked, placebo-controlled, parallel-group trial using alpha-lipoic acid infusions of 600 mg i.v. per day for 3 weeks, except for weekends, in diabetic patients with positive sensory symptoms of polyneuropathy which were scored by the Total Symptom Score (TSS) in the feet on a daily basis. Four trials (ALADIN I, ALADIN III, SYDNEY, NATHAN II) comprised n=1258 patients (alpha-lipoic acid n=716; placebo n=542) met these eligibility criteria and were included in a meta-analysis based on the intention-to-treat principle. Primary analysis involved a comparison of the differences in TSS from baseline to the end of i.v. Treatment between the groups treated with alpha-lipoic acid or placebo. Secondary analyses included daily changes in TSS, responder rates (> or =50% improvement in TSS), individual TSS components, Neuropathy Impairment Score (NIS), NIS of the lower limbs (NIS-LL), individual NIS-LL components, and the rates of adverse events. RESULTS: After 3 weeks the relative difference in favour of alpha-lipoic acid vs. placebo was 24.1% (13.5, 33.4) (geometric mean with 95% confidence interval) for TSS and 16.0% (5.7, 25.2) for NIS-LL. The responder rates were 52.7% in patients treated with alpha-lipoic acid and 36.9% in those on placebo (P<0.05). On a daily basis there was a continuous increase in the magnitude of TSS improvement in favour of alpha-lipoic acid vs. placebo which was noted first after 8 days of treatment. Among the individual components of the TSS, pain, burning, and numbness decreased in favour of alpha-lipoic acid compared with placebo, while among the NIS-LL components pin-prick and touch-pressure sensation as well as ankle reflexes were improved in favour of alpha-lipoic acid after 3 weeks. The rates of adverse events did not differ between the groups. CONCLUSIONS: The results of this meta-analysis provide evidence that treatment with alpha-lipoic acid (600 mg/day i.v.) over 3 weeks is safe and significantly improves both positive neuropathic symptoms and neuropathic deficits to a clinically meaningful degree in diabetic patients with symptomatic polyneuropathy.

Antioxidants↗
PubMed2003

Neospora caninum in sheep: a herd case report.

Neospora caninum was detected by means of PCR in the brain of 4 out of 20 aborted fetuses in a flock of 117 sheep exhibiting a persistent abortion problem, and N. caninum tissue cysts were furthermore found in encephalitic lesions in one of the PCR-positive fetuses. Toxoplasma gondii was detected as aborting agent in another 3 out of 20 fetuses. Antibodies to N. caninum (by indirect fluorescence antibody test (IFAT)) were found in 10.3% of 117 ewes and antibodies for T. gondii were found in 97.4% of 117 ewes. Other organisms associated with abortion were Chlamydia psittaci in three fetuses and Pasteurella multocida in one fetus. This is the first report of N. caninum associated abortion in naturally infected sheep.

Aborted Fetus↗
PubMed2003

Impairment of cerebral autoregulation in diabetic patients with cardiovascular autonomic neuropathy and orthostatic hypotension.

AIMS: Impaired cerebrovascular reactivity and autoregulation has been previously reported in patients with diabetes mellitus. However, the contribution of cardiovascular diabetic autonomic neuropathy and orthostatic hypotension to the pathogenesis of such disturbances is not known. The purpose of this study was to evaluate cerebral blood flow velocity in response to standing in patients with diabetes and cardiovascular autonomic neuropathy with or without orthostatic hypotension. METHODS: We studied 27 patients with diabetes--eight had cardiovascular autonomic neuropathy and orthostatic hypotension (age 46.4 +/- 13.5 years, diabetes duration 25.0 +/- 11.0 years), seven had autonomic neuropathy without hypotension (age 47.3 +/- 12.7 years, diabetes duration 26.4 +/- 12.1 years), and 12 had no evidence of autonomic neuropathy (age 44.1 +/- 13.8 years, diabetes duration 17.1 +/- 10.2 years)-and 12 control subjects (age 42.6 +/- 9.7 years). Flow velocity was recorded in the right middle cerebral artery using transcranial Doppler sonography in the supine position and after active standing. RESULTS: Cerebral flow velocity in the supine position was not different between the groups studied. Active standing resulted in a significant drop of mean and diastolic flow velocities in autonomic neuropathy patients with orthostatic hypotension, while there were no such changes in the other groups. The relative changes in mean flow velocity 1 min after standing up were -22.7 +/- 16.25% in patients with neuropathy and orthostatic hypotension, +0.02 +/- 9.8% in those with neuropathy without hypotension, -2.8 +/- 14.05% in patients without neuropathy, and -9.2 +/- 15.1% in controls. CONCLUSIONS: Patients with diabetes and cardiovascular autonomic neuropathy with orthostatic hypotension show instability in cerebral blood flow upon active standing, which suggests impaired cerebral autoregulation.

Adolescent↗
PubMed2003

IRAS splice variants.

The human I(1)-imidazoline receptor candidate gene, iras, has previously been cloned and mapped to locus 3p21.1-9 (also known as Nischarin; accession No. AC006208). By comparison to a database of expressed sequence tags (ESTs), three alternatively spliced transcripts have been deduced. A map of 21 exons was constructed for the medium-length transcript (IRAS-M) containing 5,232 base pairs (bp) and encoding 1,504 amino acids (aas). Introns 13B and 13C are inserted into the two alternative transcripts, forming IRAS-S and IRAS-L mRNA (short and long isoforms). Northern blots confirmed the existence of these mRNA isoforms. In most brain regions the order of mRNA abundance was IRAS-M > IRAS-L > IRAS-S mRNA. Although aas 1 through 510 are theoretically identical, truncated proteins could be derived from IRAS-S (2,678 bp transcript yields 515 aas) and IRAS-L (9,457 bp transcript yields 583 aas). Because exon-16 of the iras gene has been proposed to encode the functional domains of imidazoline and a-5 integrin binding, only IRAS-M is expected to possess I(1) receptor properties. Subtype-selective cDNA expression constructs were therefore generated and used to transfect CHO cells. High-affinity I(1) binding was endowed by IRAS-M and IRAS-L, but not by IRAS-S transfection.

Alternative Splicing↗
PubMed2002

[Costs for acute, stationary treatment of polytrauma patients].

Are the costs required for a polytraumatised patient sufficiently paid by the health care companies?The study population consisted of 71 polytrauma patients. The treatment-costs were calculated and compared with the reimbursements. The mean patient age was 38.0 years with a mean injury severity score (ISS) of 23.0 points. The mean duration of hospitalisation was 25.9 days and the mean calculated cost per patient was Euro 21,866.30. The reimbursement was only Euro 16,863.03/patient. This leads to a financial deficit of approximately Euro 5,000/patient (Euro 167/polytrauma patient/hospital day) and nearly Euro 355,000 for all patients during the period of 1 year. The introduction of the DRG system endangers the high standard of polytrauma treatment because of insufficient reimbursement.It is necessary to consider the implementation of an additional polytrauma-reimbursement based on the injury severity and duration of hospitalisation. The concentration of the patients in trauma centres, where the optimum of therapy is guarantied, leads in these hospitals to a continuously increasing deficit. The latter may be deleterious for the concept of "trauma centers" in the future.

Adult↗
PubMed2001

Time- and frequency-domain estimation of early diabetic cardiovascular autonomic neuropathy.

The risk related to cardiovascular autonomic neuropathy dysautonomia should lead to a specific assessment of this complication of diabetes. The aim of this study was to estimate the accuracy of a battery of blood pressure (BP) and heart rate (HR) variability indexes obtained in different subgroups of diabetic subjects classified according to the conventional laboratory autonomic function tests (Ewing scores). Blood pressure was measured continuously at the finger level with a Finapres monitor while subjects were in the supine position and again while they were standing. Pulse intervals were derived from BP recordings and were taken as surrogates for R-R intervals. Subjects with borderline or definite cardiovascular autonomic neuropathy showed a similar degree of alterations of both HR and BP variability (spectral measures) and in the relationship between BP and HR (cross-spectral and sequence analysis). Subjects with no evidence of cardiovascular autonomic neuropathy on the basis of the conventional tests showed an altered relationship between BP and HR. This baroreceptor-HR reflex dysfunction could represent an early stage of cardiovascular autonomic neuropathy undetected by the conventional tests. The areas under the receiver operating characteristic plots indicated that the high-frequency peak of pulse interval was highly discriminant in the supine and standing positions. The cross-spectral analysis showed the best discrimination for the gain in the high-frequency range. For the sequence analysis, the slope was the best discriminant factor for any degree of cardiovascular autonomic neuropathy. In conclusion, these estimates of baroreceptor-HR function may provide a powerful tool for assessing cardiovascular autonomic neuropathy at any stage, including the early stage, which is not detected by the conventional tests.

Adult↗
PubMed2001

Standardized tests of heart rate variability: normal ranges obtained from 309 healthy humans, and effects of age, gender, and heart rate.

The authors undertook this study to determine the effects of age, gender, and heart rate (HR) on the results of cardiac autonomic function tests for measuring heart rate variability (HRV) in a large sample of healthy subjects (n = 309). Conventional tests (deep breathing, maximum/minimum 30:15 ratio), and a standardized 5-minute resting study, including spectral analysis of HR, were used. The main findings included (1) the indices of all tests, except for the ratio of the low- (LF) to high-frequency (HF) spectral power (LF/HF ratio) and HR itself, are inversely related to age in both sexes; (2) the 5-minute spectral bands (except for the LF/HF ratio), the variation coefficient, expiratory-inspiratory ratio during deep breathing, and the maximum/minimum 30:15 ratio are independent of HR; (3) women up to the age of 55 years have a higher resting HR compared with men; (4) young and middle-aged women show a significantly lower LF power and LF/HF ratio compared with age-matched men, whereas no significant gender differences are observed in the absolute HF power. The authors computed age- and gender-dependent normal values for each of the HRV indices studied here and discuss the clinical consequences arising from gender differences in HRV.

Adolescent↗