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Biomedical subjects

R Wenzel

Publications and source records attributed to R Wenzel.

At least 19 recordsLinked to original sources
PubMed2005

Economic evaluation of voriconazole compared with conventional amphotericin B for the primary treatment of aspergillosis in immunocompromised patients.

OBJECTIVE: The objective of this study was to conduct an economic evaluation of voriconazole compared with conventional amphotericin B deoxycholate (CAB) using data from a recently reported randomized comparative trial in patients with various underlying immunosuppressive conditions. This trial demonstrated the superiority of voriconazole in terms of clinical response, survival and safety when used as primary therapy for invasive aspergillosis. METHODS: A decision analytic model was designed using an expert panel and populated primarily with efficacy and resource utilization data collected prospectively during the clinical trial. The analysis was carried out from the perspective of the health care system and all costs are reported in 2002 US dollars. RESULTS: Average total treatment costs per patient were 10% lower in the voriconazole arm ($30 664) than in the CAB arm ($34 144), resulting from reduced consumption of hospital resources and fewer changes in antifungal therapy. In the base case analysis, voriconazole provided an average saving of $3481 per treated patient, resulted in a lower cost per survivor ($43 310 versus $58 971) and a lower cost per successfully treated patient ($58 100 versus $108 124) compared with CAB. Sensitivity analyses demonstrated that the cost savings observed were maintained over a wide range of alternative values for both unit costs and resource utilization, including length of hospital stay, time spent in intensive care units, bed day costs and the cost of lipid formulations of amphotericin B. CONCLUSION: Incremental cost-effectiveness analysis indicated the dominance of voriconazole because of both lower costs and greater efficacy.

Amphotericin B↗
PubMed2003

Malignant peripheral nerve sheath tumours in neurofibromatosis type 1: MRI supports the diagnosis of malignant plexiform neurofibroma.

Plexiform neurofibroma (PNF) is a typical feature of neurofibromatosis 1 (NF1). About 10% of patients with NF1 develop malignant peripheral nerve-sheath tumours (MPNST), usually arising from PNF, and this is the major cause of poor survival. A better prognosis can be achieved if the tumours are diagnosed at an early stage. Our objective was to establish MRI criteria for MPNST and to test their usefulness in detecting early malignant change in PNF. MRI was performed on 50 patients with NF1 and nerve-sheath tumours, of whom seven had atypical pain, tumour growth or neurological deficits indicative of malignancy; the other 43 were asymptomatic. On MRI all seven symptomatic patients had inhomogeneous lesions, due to necrosis and haemorrhage and patchy contrast enhancement. In one patient, the multiplicity of confluent tumours with inhomogeneous areas in addition to central lesions did not allow exclusion of malignancy. Only three of the 43 asymptomatic patients had comparable changes; the other 40 patients had tumours being of relatively homogeneous structure on T1- and T2-weighted images before and after contrast enhancement. All three asymptomatic patients with inhomogeneous lesions were shown to have MPNST.

Adolescent↗
PubMed2001

Linear aspects of changes in deoxygenated hemoglobin concentration and cytochrome oxidase oxidation during brain activation.

We used near infrared spectroscopy (NIRS) to investigate the vascular and metabolic response to brain activation in human primary and adjacent secondary visual cortex. NIRS is able to measure concentration changes in deoxygenated hemoglobin ([deoxy-Hb]) (which mainly contribute to the blood oxygenation level-dependent (BOLD) signal in functional magnetic resonance imaging (fMRI)) as well as concentration changes of oxygenated hemoglobin ([oxy-Hb]) and corpuscular blood volume ([total-Hb] = [oxy-Hb] + [deoxy-Hb]) and changes in the redox status of the cytochrome c oxidase ([Cyt-Ox]), a putative parameter for cellular oxygenation. A sound understanding of the transfer functions between stimulus parameters, neuronal activity, and vascular/metabolic parameters is important for interpretation of data acquired with indirect neuroimaging techniques like fMRI, especially in event-related design studies. In the present study we tested whether the vascular/metabolic response to stimulation can be described as a linear and time invariant system. Since linearity is a property attributed to systems that satisfy the scaling and superposition properties, as a first simple test, superposition of the responses obtained from short duration visual stimuli was used to predict the responses of longer duration stimuli. Our results showed that the predictions of [deoxy-Hb] and [Cyt-Ox] responses to stimuli of 6- to 24-s duration were satisfactory whereas predictions of [oxy-Hb] and [total-Hb] were insufficient. In a second step, a calculated convolution function of an assumed impulse response function and the stimulus function was fitted with the measured [deoxy-Hb] and [Cyt-Ox] curves to obtain amplitude, time delay, and time constant parameters. We show that predictions of cellular and vascular oxygenation responses to visual stimulation are good for 6- to 24-s stimuli duration under the assumption of a linear transfer characteristic. This model is not valid for corpuscular volume changes which affect mainly the [oxy-Hb] response. Noninvasive NIRS is shown to be a suitable method to get more direct information about neuronal-activity-associated changes in cerebral parameters which are partly reflected in BOLD signal but are not fully understood yet.

Adult↗
PubMed2001

Simultaneous near-infrared spectroscopy monitoring of left and right occipital areas reveals contra-lateral hemodynamic changes upon hemi-field paradigm.

In this study we have shown that in humans it is possible to monitor non-invasively and simultaneously both hemispheres revealing cortical oxygenation changes in the occipital area in response to a contra-lateral hemi-field paradigm. A novel multi-channel near infrared spectroscopy approach with a high temporal resolution was used. The results confirm previous findings obtained by functional magnetic resonance imaging and positron emission tomography with the advantage to measure directly not only concentration changes in deoxyhemoglobin as measured by functional magnetic resonance imaging (MRI), but also in oxyhemoglobin with low cost instrumentation potentially useful to investigate the pathophysiology of vision.

Adult↗
PubMed2000

Spontaneous low frequency oscillations of cerebral hemodynamics and metabolism in human adults.

UNLABELLED: We investigated slow spontaneous oscillations in cerebral oxygenation in the human adult's visual cortex. The rationale was (1) to demonstrate their detectability by near infrared spectroscopy (NIRS); (2) to analyze the spectral power of as well as the phase relationship between the different NIRS parameters (oxygenated and deoxygenated hemoglobin and cytochrome-oxidase; oxy-Hb/deoxy-Hb/Cyt-ox). Also (3) influences of functional stimulation and hypercapnia on power and phase shifts were investigated. The results show that-in line with the literature-low frequency oscillations (LFO) centred around 0.1 s(-1) and even slower oscillations at about 0.04 s(-1) (very low frequency, VLFO) can be distinguished. Their respective power differs between oxy-Hb, deoxy-Hb, and Cyt-ox. Either frequency (LFO and VLFO) is altered in magnitude by functional stimulation of the cortical area examined. Also we find a change of the phase shift between the vascular parameters (oxy-Hb, tot-Hb) and the metabolic parameter (Cyt-ox) evoked by the stimulation. It is shown that hypercapnia attenuates the LFO in oxy-Hb and deoxy-Hb. CONCLUSIONS: (1) spontaneous vascular and metabolic LFO and VLFO can be reproducibly detected by NIRS in the human adult. (2) Their spectral characteristics and their response to hypercapnia are in line with those described in exposed cortex (for review see (Hudetz et al., 1998)) and correspond to findings with transcranial doppler sonography (TCD) (Diehl et al., 1995) and fMRI (Biswal et al., 1997). (3) The magnitude of and phase relation between NIRS-parameters at the LFO may allow for a local noninvasive assessment of autoregulatory mechanisms in the adult brain.

Adult↗
PubMed2000

Gadolinium-myelocisternography for cerebrospinal fluid rhinorrhoea.

Knowledge of the exact site of leakage of cerebrospinal fluid CSF leakage is important for planning surgery. We report our experience with myelocisternography with Gd-DTPA. We decided that intrathecal use of this contrast medium was justified in selected cases when other techniques have failed. After we had given detailed information to four patients with CSF leakage, they underwent five examinations. The images were interpreted by comparing those before and after injection. In all cases the contrast medium arrived at the basal cisterns, giving high contrast against adjacent structures. All patients tolerated the examination without complications or any indication of side effects.

Adult↗
PubMed2000

Near-infrared spectroscopy: does it function in functional activation studies of the adult brain?

Changes in optical properties of biological tissue can be examined by near-infrared spectroscopy (NIRS). The relative transparency of tissues including the skull to near-infrared light is the prerequisite to apply the method to brain research. We describe the methodology with respect to its applicability in non-invasive functional research of the adult cortex. A summary of studies establishing the 'typical' response in NIRS vascular parameters, i.e. changes in the concentration of oxygenated and deoxygenated haemoglobin, over an activated area is followed by the validation of changes in the cytochrome-oxidase redox state in response to a visual stimulus. Proceeding from these findings a rough mapping of this metabolic response over the motion-sensitive extrastriate visual area is demonstrated. NIRS measures concentration changes in deoxygenated haemoglobin [deoxy-Hb] which are assumed to be the basis of fMRI BOLD contrast (blood oxygenation level-dependent). The method is therefore an excellent tool to validate assumptions on the physiological basis underlying the fMRI signal, due to its high specificity as to the parameters measured. Questions concerning the concept of 'activation'/'deactivation' and that of the linearity of the vascular response are discussed. To challenge the method we finally present results from a complex single-trial motor paradigm study testing the hypothesis, that premotor potentials (contingent negative variation) can be examined by functional techniques relying on the vascular response. Some of the work described here has been published elsewhere.

Adult↗
PubMed2000

Saccadic suppression induces focal hypooxygenation in the occipital cortex.

This study investigated how a decrease in neuronal activity affects cerebral blood oxygenation employing a paradigm of acoustically triggered saccades in complete darkness. Known from behavioral evidence as saccadic suppression, electrophysiologically it has been shown in monkeys that during saccades an attenuation of activity occurs in visual cortex neurons (Duffy and Burchfiel, 1975). In study A, using blood oxygen level-dependent (BOLD) contrast functional magnetic resonance imaging (fMRI), the authors observed signal intensity decreases bilaterally at the occipital pole during the performance of saccades at 2 Hz. In study B.1, the authors directly measured changes in deoxyhemoglobin [deoxy-Hb] and oxyhemoglobin [oxy-Hb] concentration in the occipital cortex with near-infrared spectroscopy (NIRS). Whereas a rise in [deoxy-Hb] during the performance of saccades occurred, there was a drop in [oxy-Hb]. In a second NIRS study (B.2), subjects performed saccades at different rates (1.6, 2.0, and 2.3 Hz). Here the authors found the increase in deoxy-Hb and the decrease of oxy-Hb to be dependent on the frequency of the saccades. In summary, the authors observed a focal hypooxygenation in the human visual cortex dependent on the saccade-frequency in an acoustically triggered saccades paradigm. This could be interpreted as evidence that corresponding to the focal hyperoxygenation observed in functional brain activation, caused by an excessive increase in cerebral blood flow (CBF) over the increase in CMRO2 during decreased neuronal activity CBF, is more reduced than oxygen delivery.

Acoustic Stimulation↗
PubMed2000

Endothelin-1 contributes to hyperoxia-induced vasoconstriction in the human retina.

PURPOSE: There is evidence that ocular blood flow strongly depends on arterial oxygen tension. Results from recent animal studies indicate that the vasoconstrictor response to hyperoxia may be mediated in part by an increased production of endothelin (ET)-1. In an effort to answer the question whether the retinal vasoconstrictive response to hyperoxia in humans is mediated through ET-1, changes in ocular hemodynamics induced by 100% O2 breathing were studied in the absence and presence of an ET(A) receptor antagonist (BQ-123). METHODS: The study was a randomized, placebo-controlled, double-masked, balanced, three-way crossover design. On separate study days 15 healthy male subjects received infusions of BQ-123 (either 60 microg/min or 120 microg/min) or placebo. The effects of BQ-123 or placebo on hyperoxia-induced (100% O2 breathing) changes in retinal and pulsatile choroidal blood flow were assessed with the blue-field entoptic technique and with laser interferometric measurement of fundus pulsation, respectively. RESULTS: During baseline conditions, hyperoxia caused a decrease in retinal blood flow between -29% and -34% (P<0.001) and a decrease in fundus pulsation amplitude between -7% and -8% (P<0.001). BQ-123 dose dependently blunted the response to hyperoxia in the retina (60 microg/min: -25%, 120 microg/min: -20%; P = 0.003), but not in the choroid. CONCLUSIONS: These results indicate that ET-1 contributes to hyperoxia-induced retinal vasoconstriction in the human retina.

Adult↗
PubMed1999

The return of tuberculosis.

At the end of the 20th century, tuberculosis remains a major public health issue. In developing countries tuberculosis is a leading cause of morbidity and mortality, and the spread of the HIV epidemic contributes significantly to the worsening of the situation. Coinfection with tuberculosis and HIV results in special diagnostic and therapeutic problems and uses up larger amounts of medical resources in developing countries. Outbreaks of multidrug resistant tuberculosis (MDR-TB) were first reported from US-American centers caring for HIV patients, but have now been observed in many other countries. In Western Europe the tuberculosis epidemic is under control, but increasing incidence rates in migrants raise new problems in these countries. Tuberculosis is uncontrolled in large parts of the former Soviet Union due to the socio-economic break-down in these countries. Only rigorous infection control measures on a world-wide scale will prevent further detoriation of this situation. Therefore, the extension of surveillance systems, and sufficient funding for the prevention, diagnosis, and treatment of tuberculosis by national governments and international organizations are all urgently needed.

AIDS-Related Opportunistic Infections↗
PubMed1999

Noninvasive assessment of changes in cytochrome-c oxidase oxidation in human subjects during visual stimulation.

In this study the authors used a whole-spectrum near-infrared spectroscopy approach to noninvasively assess changes in hemoglobin oxygenation and cytochrome-c oxidase redox state (Cyt-Ox) in the occipital cortex during visual stimulation. The system uses a white light source (halogen lamp). The light reflected from the subject's head is spectrally resolved by a spectrograph and dispersed on a cooled charge-coupled device camera. The authors showed the following using this approach: (1) Changes in cerebral hemoglobin oxygenation (increase in concentration of oxygenated hemoglobin, decrease in concentration of deoxygenated hemoglobin) in the human occipital cortex during visual stimulation can be assessed quantitatively. (2) The spectral changes during functional activation cannot be completely explained by changes in hemoglobin oxygenation solely; Cyt-Ox has to be included in the analysis. Only if Cyt-Ox is considered can the spectral changes in response to increased brain activity be explained. (3) Cytochrome-c oxidase in the occipital cortex of human subjects is transiently oxidized during visual stimulation. This allows us to measure vascular and intracellular energy status simultaneously.

Adult↗
PubMed1997

Cerebral haemoglobin oxygenation during sustained visual stimulation--a near-infrared spectroscopy study.

Using near-infrared spectroscopy, we investigated the time-course of the concentrations of oxygenated haemoglobin, [oxy-Hb], and deoxygenated haemoglobin [deoxy-Hb], in the occipital cortex of healthy human adults during standard sustained visual stimulation. Within a few seconds after stimulation (by coloured dodecahedron), we observed a decrease in [deoxy-Hb], peaking after 13 s ('initial undershoot'). In the subsequent 1-2 min, in seven out of ten subjects, [deoxy-Hb] gradually returned to a plateau closer to the baseline level. After cessation of stimulation, there was a 'post-stimulus overshoot' in [deoxy-Hb]. There was a statistically significant correlation between the size of the 'initial undershoot' and the post-stimulus overshoot'. The concentration of oxyhaemoglobin increased upon functional activation. However, in the mean across all subjects there was no 'initial overshoot'. After approximately 19 s it reached a plateau and remained constantly elevated throughout the activation period. After cessation of activation there was a 'post-stimulus undershoot' of oxyhaemoglobin. It is important to consider the time-course of haemoglobin oxygenation when interpreting functional activation data, especially those data obtained with oxygenation-sensitive methods, such as BOLD-contrast fMRI.

Adult↗
PubMed1997

Decrease in parietal cerebral hemoglobin oxygenation during performance of a verbal fluency task in patients with Alzheimer's disease monitored by means of near-infrared spectroscopy (NIRS)--correlation with simultaneous rCBF-PET measurements.

We used near-infrared spectroscopy (NIRS) to study non-invasively changes in cerebral hemoglobin oxygenation in the frontal and parietal cortex during performance of a verbal fluency task in patients with Alzheimer's disease (AD). Whereas healthy elderly subjects (n = 19, age 67 +/- 10 years) showed increases in concentrations of oxygenated hemoglobin [HbO2] (mean (arbitrary units) +/- S.E.M., 1.44 +/- 0.59) and total hemoglobin [HbT] (0.92 +/- 0.81) over the left superior parietal cortex, patients with AD (n = 19, age 71 +/- 10 years) showed significant decreases in [HbO2] (-3.26 +/- 1.30, P < 0.01) as well as [HbT] (-4.45 +/- 1.57, P < 0.01). [HbR] decreased slightly in both groups (-0.62 +/- 0.29 and - 1.18 +/- 0.40, respectively). Using two pairs of NIRS optodes placed on the left superior partietal cortex and on the left prefrontal cortex simultaneous increases in [HbO2] as well as [HbT] in both cortical regions in the healthy elderly subjects (n = 8, age 60 +/- 15) were demonstrated during performance of the task. AD patients (n = 10, age 65 +/- 13 years) showed decreases in [HbO2] and [HbT] in the parietal cortex and, at the same time, increases in [HbO2] and [HbT] in the frontal cortex. Simultaneous NIRS-[HbT] and PET-rCBF measurements showed a significant correlation both when calculated in a 'banana' shaped volume approximated by using cortical thresholds as well as when calculated in a semisphere volume of brain tissue beneath the optodes placed on the head surface (patients with AD, n = 10). The correlation was dependent on the assumed penetration depth of the near-infrared light and was best for all three NIRS variables ([HbO2], [HbR] and [HbT]) when calculated using a semisphere radius of 0.45 cm to 1.35 cm. In conclusion, in Alzheimer's disease a marked reduction of regional cerebral blood flow and cerebral hemoglobin oxygenation may occur during activation of brain function, probably mainly in degenerating brain areas, such as the parietal cortex.

Aged↗
PubMed1997

Length of resting period between stimulation cycles modulates hemodynamic response to a motor stimulus.

The influence of different lengths of the pre-stimulation resting period on the magnitude of a hemodynamic response evoked by motor stimulation was examined in 10 subjects by means of near-infrared spectroscopy (NIRS). A motor stimulus was used which has been previously established as a model for functional activation studies with NIRS. Subjects performed a 20 s finger opposition task in the hand contralateral to NIRS probe localization over left sensorimotor area (C3', according to the 10-20 system). The duration of the pre-stimulation resting period was varied from 10s to 50s and response magnitude was assessed for each of the interstimulus intervals (10 s, 20 s, 30 s, 40 s and 50 s). Data analysis showed that response magnitude in oxygenated and deoxygenated haemoglobin concentration changed with different interstimulation intervals. Interestingly the greatest NIRS response was obtained with resting period 30 s prior to stimulation; shorter and longer resting periods resulted in smaller responses. The time course and the dependence of response magnitude on interstimulus interval differed between [oxy-Hb] and [deoxy-Hb] changes. For [oxy-Hb] the previously described fast initial increase ('overshoot') and the post-stimulation undershoot was more clearly seen with long prestimulation resting periods. Cytochromeoxidase oxygenation changes did not change significantly with different interstimulus intervals. We conclude that comparisons between different functional activation studies with techniques relying on stimulus evoked changes in cerebral hemodynamics must take into account not only the quality of the experimental paradigm and the length of the stimulation period, but also that the resting period between repetitive stimulations is important for response amplitude and its time course.

Brain↗