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Biomedical subjects

A Kluge

Publications and source records attributed to A Kluge.

At least 19 recordsLinked to original sources

Further evidence of pleiotropy influencing speech and language: analysis of the DYX8 region.

BACKGROUND/AIMS: Genetic studies have raised the possibility of common bases for cognitive linguistic disorders such as speech sound disorder (SSD), reading disorder (RD) and language impairment (LI). Thus, some of the same genes may jointly influence cognitive components within and between these three disorders. We examined the plausibility of this theory in a sample of families ascertained on the basis of a child with SSD. METHODS: Using the method of generalized estimating equations to solve a bivariate family predictive model we obtained measures of comorbidity and familial aggregation of SSD and LI. We then used two methods of multipoint model-free linkage analysis to evaluate SSD and LI psychometric test measures over a region previously implicated in linkage studies of RD, DYX8 region, 1p34-p36. RESULTS: Bivariate phenotypic analyses show evidence of comorbidity and within family aggregation and coaggregation of SSD and LI. In addition, two regions on chromosome 1 show suggestive evidence of linkage. The first region was previously reported in dyslexia studies. Our maximum linkage signal in this region measured articulation (p = 0.0009) in SSD sibling pairs. The second region is characterized by processes involved in language production, with the maximum linkage signal measuring listening comprehension (p = 0.0019) using all sibling pairs. CONCLUSION: We conclude that the DYX8 region could bear genes controlling pleiotropic effects on SSD, LI and RD.

Articulation Disorders↗

[Improvement of anxiety and depression in women with breast cancer during inpatient oncological rehabilitation-- results of a prospective study].

PURPOSE: Investigation of the influence of an oncological inpatient rehabilitation programme on anxiety and depression in women with breast cancer. PATIENTS AND METHOD: 198 women with breast cancer, aged 25 to 75 years, filled in the Hospital Anxiety and Depression Scale (HADS) German version at the beginning and end of inpatient rehabilitation. Focus was set on the frequency of anxiety and depression. Therefore proportions with 95 % confidence intervals (CI) were built. The before-after comparison of HADS-scores was made using the signed rank test with two-sided level of significance of alpha = 5 %. In addition effect sizes were calculated. Possible relations between the scores at the beginning of rehabilitation and the patients' age or the interval since diagnosis were analysed by calculating correlation coefficients. RESULTS: At the beginning of rehabilitation a state of anxiety was probable in 23.2 % (CI [17.3 %; 29.1 %] of the women and one of depression in 9.1 % (CI [5.8 %; 13.9 %]). In other words, they reached a level of >or= 11 score points on each scale. No correlation was found with the age of the patients or the time interval since diagnosis (|r| <or= 0.192). At the end of rehabilitation 67.5 % (CI [61.0 %; 74.0 %]) and 60.9 % (CI [54.1 %; 67.7 %]), respectively, of the women showed an improvement of anxiety and depression. The before-after difference was a median + 2 points (anxiety) and + 1 point (depression), resp., with a positive value representing an improvement. The changes after rehabilitation were statistically significant with p < 0.0001. The effect sizes ranged from 0.37 to 0.50. CONCLUSIONS: After the end of primary therapy, women with breast cancer frequently suffer from anxiety or depressive disorders, with no correlation to the patients' age or time since diagnosis. By an inpatient oncological rehabilitation programme both anxiety and depression can be improved very successfully. Whether these results represent a long-term effect is currently being evaluated in a randomised prospective study.

Adult↗

Pulmonary perfusion in acute pulmonary embolism: agreement of MRI and SPECT for lobar, segmental and subsegmental perfusion defects.

PURPOSE: To assess prospectively the agreement of magnetic resonance (MR) pulmonary perfusion with single-photon emission computed tomography (SPECT) perfusion for perfusion defects down to the subsegmental level in patients with suspected pulmonary embolism (PE). MATERIAL AND METHODS: In 41 patients with suspected PE, contrast-enhanced MR pulmonary perfusion (3D-FLASH, TR/TE 1.6/0.6 ms) was compared to SPECT perfusion on a per-examination basis as well as at the lobar, segmental, and subsegmental level. RESULTS: The MRI protocol was completed in all patients, and mean examination time was 3 min 56 s. MR perfusion showed a very high agreement with SPECT (kappa value per examination 0.98, and 0.98, 0.83, and 0.69 for lobar, segmental, and subsegmental perfusion defects, respectively). Of 15 patients with PE, MR perfusion detected 14 cases. CONCLUSION: The very high agreement of MR perfusion with SPECT perfusion enables the detection of subtle findings in suspected PE.

Acute Disease↗

[Thoracic real-time MRI: experience from 2200 examinations in acute and ill-defined thoracic diseases].

PURPOSE: To retrospectively assess the indication for thoracic real-time MRI, demonstrate typical findings, analyze the diagnostic potential in subgroups with suspected pulmonary embolism (PE) and aortic dissection (AD), and describe the influence of real-time MRI on the role of MRI in acute thoracic diseases. MATERIALS AND METHODS: From July 2001 to February 2005, real-time MRI was applied in 2,256 examinations in 1,714 patients. MRI was the primary diagnostic modality for these thoracic diseases as computed tomography has been available only since 2003. Characteristics of the TrueFISP sequence applied were: TR/TE/flip angle 3.1 ms/1.6 ms/59 degrees , respectively. FOV 340 - 360 mm, matrix size 156 to 192 x 256 pixels, slice thickness 3 to 4 mm, slices overlapped by 50 %. Acquisition time was 0.4 to 0.5 s per image. Three hundred and twenty transverse, coronal and sagittal images were acquired in three minutes. No breath holding, and only minimal patient cooperation, was required. Turbo-spin-echo sequences as well as ECG-gated and contrast-enhanced sequences were added depending on the indication. RESULTS: Most common indications were: acute thoracic nonspecified disease (n = 276, 12.24 %), PE (n = 573, 25.4 %), bleeding (n = 154, 6.8 %), AD (n = 222, 9.8 %), topographic information in complex findings (n = 654, 29.0 %). Real-time MRI was the sole MRI technique applied in 180 examinations (8.0 %), ECG-gated real-time MRI was applied in 87 examinations and breath hold was used in 107 examinations. PE was diagnosed in 181 examinations; reference techniques (MRI, computed tomography, single photon emission computed tomography) confirmed 170 of these and detected 19 more cases (sensitivity 90.0 %, specificity 97.1 %). Real-time MRI detected 141 suspected AD and 53 more nonsuspected AD. Of these, 191 were confirmed by other MRI techniques, surgery or clinical course (98.5 %). Real-time MRI coincidentally detected 56 pulmonary tumors, all were confirmed with computed tomography. Thus, especially vascular diseases could be easily assessed with real-time MRI, while computed tomography had advantages in the evaluation of the lung parenchyma. CONCLUSION: Real-time MRI both enables emergency MRI examinations for thoracic diseases in clinical patients in unstable condition and allows an explorative style of working in patients with nondefined acute thoracic diseases.

Acute Disease↗

The pharmacokinetics of zinc from zinc gluconate: a comparison with zinc oxide in healthy men.

OBJECTIVE: Zinc supplementation is beneficial in some clinical conditions such as age-related macula degeneration (AMD). It has been suggested that zinc absorption is influenced by the form in which zinc is ingested. Therefore, the pharmacokinetics of zinc gluconate (organic) were compared with those of zinc oxide (inorganic). METHODS: 12 healthy male subjects aged between 21 and 31 years (24 years median) orally received daily doses of 20 mg metal zinc as zinc gluconate and 17.4 mg metal zinc as zinc oxide under randomized crossover conditions for 14 days each with at least 14 days as a washout. Zinc plasma concentrations were measured by means of inductively coupled plasma-atomic emission spectroscopy. RESULTS: C(max) was found 18.3% (10.3 - 26.3%) higher following multiple-dose administration of zinc gluconate as compared to zinc oxide (mean; 0.95% confidence interval of the relative differences between both treatment conditions; p < 0.05). AUC(0-24h) was noted 8.1% (1.9 - 14.3%) higher after zinc was given as zinc gluconate when compared to zinc oxide (p < 0.05) whereas t(max) did not differ between both treatment conditions. CONCLUSIONS: Zinc absorption in humans could be improved by zinc complexation with gluconate.

Adult↗

Ankylosing spondylitis and bone mineral density--what is the ideal tool for measurement?

Ankylosing spondylitis (AS) is characterised by chronic inflammation and partial ossification, yet vertebral fractures due to osteoporosis, although common, are frequently unrecognised. The aim of this study was to (1) show the frequency of changes in the progress of osteopenia/osteoporosis in AS depending on duration and stage of the disease and (2) assess the ranking of two different methods of bone density measurement in this clinical pattern. We measured bone density in 84 male and female patients with both dual X-ray absorptiometry (DXA) and single energy quantitative computed tomography (SE-QCT). In the initial and advanced stages of the disease, a high decrease in axial bone density could be verified (DXA: osteopenia in 5% and osteoporosis in 9.2%; SE-QCT: osteopenia in 11.8% and osteoporosis in 30.3%). Peripheral bone density decrease as in osteopenia could be proven in 17.6% by DXA measurement. With SE-QCT, a decrease in vertebral trabecular bone density could already be observed in the initial stage and continued steadily during the course of the disease; cortical bone displayed the same trend up to stages of ankylosis. With DXA, valid conclusions are more likely to be expected in less marked ankylosing stages of AS. In stages of advanced ankyloses in the vertebral region (substantial syndesmophytes), priority should be given to SE-QCT, due to the selective measurement of trabecular and cortical bone. The DXA method often yields values that are too high, and the replacement of vertebral trabecular bone by fatty bone marrow is not usually recorded as standard. There may already be an increased risk of bone fracture in AS in osteopenia on DXA along with an osteoporosis already established on SE-QCT.

Absorptiometry, Photon↗

Phase- and size-adjusted CT cut-off for differentiating neoplastic lesions from normal colon in contrast-enhanced CT colonography.

A computed tomography (CT) cut-off for differentiating neoplastic lesions (polyps/carcinoma) from normal colon in contrast-enhanced CT colonography (CTC) relating to the contrast phase and lesion size is determined. CT values of 64 colonic lesions (27 polyps <10 mm, 13 polyps > or =10 mm, 24 carcinomas) were determined by region-of-interest (ROI) measurements in 38 patients who underwent contrast-enhanced CTC. In addition, the height (H) of the colonic lesions was measured in CT. CT values were also measured in the aorta (A), superior mesenteric vein (V) and colonic wall. The contrast phase was defined by xA + (1-x)V using x as a weighting factor for describing the different contrast phases ranging from the pure arterial phase (x=1) over the intermediate phases (x=0.9-0.1) to the pure venous phase (x=0). The CT values of the lesions were correlated with their height (H), the different phases (xA+(1-x)V) and the ratio [xA+(I-x)V]/H. The CT cut-off was linearly adjusted to the imaged contrast phase and height of the lesion by the line y=m[xA+(1-x)V]H+y(0). The slope m was determined by linear regression in the correlation (lesion approximately [xA+(i-x)V]/H) and the Y-intercept y(0) by the minimal shift of the line needed to maximize the accuracy of separating the colonic wall from the lesions. The CT value of the lesions correlated best with the intermediate phase: 0.4A + 0.6V (r=0.8 for polyps > or =10 mm, r=0.6 for carcinomas, r=0.4 for polyps <10 mm). The accuracy in the differentiation between lesions and normal colonic wall increased with the height implemented as divisor, reached 91% and was obtained by the dynamic cut-off described by the formula: cut-off (A,V,H)=1.1 [0.4A+0.6V]/H+69.8. The CT value of colonic polyps or carcinomas can be increased extrinsically by scanning in the phase in which 0.4A + 0.6V reaches its maximum. Differentiating lesions from normal colon based on CT values is possible in contrast-enhanced CTC and improves when the cut-off is adjusted (normalized) to the contrast phase and lesion size.

Adult↗

Noninvasive quantification of brain edema and the space-occupying effect in rat stroke models using magnetic resonance imaging.

BACKGROUND AND PURPOSE: Brain edema is a life-threatening consequence of stroke and leads to an extension of the affected tissue. The space-occupying effect due to brain edema can be quantified in rat stroke models with the use of MRI. The present study was performed to test 2 hypotheses: (1) Can quantification of the space-occupying effect due to brain edema serve as a noninvasive measure for brain water content? (2) Does morphometric assessment of brain swelling allow determination of true infarct size on MRI after correction for the space-occupying effect of edema? METHODS: Thirty rats were subjected to permanent suture middle cerebral artery occlusion. MRI was performed after 6 or 24 hours, and hemispheric swelling was assessed morphometrically. Interobserver and intraobserver agreements were determined for MRI measurements. In study I, the space-occupying effect due to brain edema was correlated with the absolute brain water content by the wet/dry method. In study II, lesion volumes corrected and uncorrected for edema were calculated on MRI and on TTC staining and compared. RESULTS: Interobserver and intraobserver agreements for MRI measurements were excellent (r>or=0.97). Brain water content and hemispheric swelling correlated well after 6 and 24 hours (r>or=0.95). Corrected lesion volumes correlated with r=0.78 between TTC staining and MRI. Without edema correction, lesion volumes were overestimated by 20.3% after 6 hours and by 29.6% after 24 hours of ischemia. CONCLUSIONS: Morphometric assessment of hemispheric swelling on MRI can determine the increase in absolute brain water content noninvasively and can also provide ischemic lesion volumes corrected for brain edema.

Animals↗

[Biventricular MR volumetric analysis and MR flow quantification in the ascending aorta and pulmonary trunk for quantification of valvular regurgitation].

PURPOSE: To test the value of biventricular volumetric analysis and the combination of biventricular volumetric analysis with flow quantification in the ascending aorta (Ao) and pulmonary trunk (Pu) for quantification of regurgitation volume and cardiac function in valvular regurgitation (VR) according to location and presence of single or multivalvular disease. MATERIALS AND METHODS: In 106 patients, the stroke volumes were assessed by measuring the biventricular volumes and the forward-stroke volumes in the great and small circulation by measuring the flow in the Ao and Pu. Valve regurgitation volumes and quotients were calculated for single and multivalvular disease and correlated with semiquantitative 2D-echocardiography (grade I-IV). For the assessment of the cardiac function in VR, the volumetric parameters of ejection fraction and end-diastolic (EDV) and end-systolic (ESV) volumes were determined. RESULTS: The detection rate was 49% for left ventricular (LV) VR and 42% for right ventricular (RV) VR. Low LV VR and RV VR usually could not be detected quantitatively, with the detection rate improving with echocardiographically higher insufficiency grades. Quantitative MRI could detect a higher grade solitary aortic valve insufficiency (> or = 2) in 11 of 12 patients and higher grade mitral valve insufficiency in 4 of 10 patients. A significant increase in RV and LV ventricular EDV and ESV was seen more often with increased MR regurgitation volumes. Aortic stenosis did not interfere with flow measurements in the Ao. CONCLUSIONS: Biventricular volumetry combined with flow measurements in Ao and Pu is a robust, applicable and simple method to assess higher grade regurgitation volumes and the cardiac function in single and multivalvular regurgitation at different locations. It is an important application for the diagnosis of VR by MRI.

Adolescent↗

[Indirect MR venography: contrast medium protocols, postprocessing and combination in diagnosing pulmonary emboli with MRI].

PURPOSE: Integration of MR venography in a comprehensive MR imaging protocol in patients with suspected pulmonary embolism (PE) and evaluation of contrast media dosage, timing and postprocessing for diagnostic accuracy. MATERIALS AND METHODS: Forty-eight consecutive inpatients with suspected PE or deep vein thrombosis were examined by MR venography according to one of the following protocols: protocol I: MR venography only, 0.25 mmol/kg body weight (BW) Gadopentate dimeglumine (Gd-DTPA) as single dose, bolus timing; protocol II: MR angiography of pulmonary arteries with a cumulative dosage of 0.25 mmol/kg contrast media, modification of coil setting for MR venography without further contrast media application; protocol III: as protocol II but with 0.125 mmol/kg BW, followed by MR venography. Signal-to-noise ratio, contrast-to-noise ratio, number of definable vascular segments and image quality were evaluated. The results were compared to conventional bilateral venography. RESULTS: All MR venography examinations were of diagnostic quality and the examination time was below 10 min. MR venography could be performed in all 48 patients compared to 43 of 48 patients for conventional venography. Significantly more superficial and deep veins of the leg could be visualized by MR venography (94 % compared to 83 % for conventional venography). Sensitivity and specificity were 100 % and 92 %, respectively. Quality differed significantly between 0.125 mmol/kg (protocol III) and 0.25 mmol/kg Gd-DTPA (protocols I and II) while timing did not influence quality (protocol I vs. II). CONCLUSION: An integrated MR diagnostic evaluation of pulmonary arteries and veins of the leg is feasible in patients with suspected PE. MR venography with 0.25 mmol/kg Gd-DTPA reliably depicts the venous system of the leg more completely than conventional venography with at least equivalent diagnostic confidence.

Adult↗

Synthesis of 2-[18F]fluoro-L-tyrosine via regiospecific fluoro-de-stannylation.

2-[18F]Fluoro-L-tyrosine is a fluorine labelled amino acid, known to be incorporated into newly synthesised proteins, rendering it a potentially suitable tracer to image protein metabolism in vivo using positron emission tomography. For the electrophilic preparation of 2-[18F]fluoro-L-tyrosine three protected 2-trialkylstannyl tyrosine derivatives have been synthesised for the first time as precursors. While O,N-di-Boc-2-triethylstannyl-L-tyrosine ethylester has proved to be suitable as precursor for radiosynthesis, imidazolidinon-derivatives of 2-triaklylstannyl tyrosine have not because of difficult fast hydrolysis of a phenolic O-methyl protective group. The di-Boc-tin derivative of tyrosine ethylester readily reacted with [18F]F2, which was prepared via the 18O(p,n)18F nuclear reaction. 2-[18F]Fluoro-L-tyrosine was isolated after full deprotection with aqueous hydrobromic acid and HPLC purification with activities of 1.41 +/- 0.32GBq. The isomeric and enantiomeric purity is high (both >99%). The preparation procedure is facile and easy to automate. The chemical yields of this fluoro-de-stannylation reaction as well as of the synthesis of 6-[18F]fluoro-L-dopa, determined with an analogous precursor and non-radioactive fluorine under identical conditions, amounted to 42.7 +/- 1.6% and 60.2 +/- 2.8%, respectively.

Journal Article↗

[Comparison between biventricular cine MRI and MR flow quantification in ascending aorta and pulmonary outflow tract for the assessment of intracardial shunt volumes].

PURPOSE: Comparison between biventricular volumetric measurements and flow measurements in ascending aorta (Ao) and pulmonary outflow tract (Pu) for quantification of intracardial shunts, and evaluation of the combination of biventricular cine MRI with flow measurements for the assessment of RV and LV heart failure and valvular regurgitation (VR). MATERIAL AND METHODS: In 24 patients, right (RV) and left (LV) ventricular volumetric and flow measurements were performed in the Ao and Pu to assess the ratio of RV stroke volume (SV) or, respectively, pulmonary SV to LV SV or, respectively, systemic aortic SV (Qp/Qs). 34 patients without echocardiographically proven shunt or VR served as control group for measurement accuracy. Left-to-right shunt ratios were calculated from RV and LV SV, Pu and Ao SV, Pu and LV SV, and RV and Ao SV. Left ventricular VR was calculated by the difference of LV SV and Ao SV, and right ventricular VR by the difference of RV SV and Pu SV. Global systolic function was evaluated by biventricular cine MRI. RESULTS: Intracardial shunts with Qp/Qs > 1.16 can be quantified by flow measurements in Ao and Pu. Using biventricular volumetric measurements in cases without VR, requires a Qp/Qs > 1.21. 17 of 18 intracardiac shunts were identified on MRI, and all 8 hemodynamically significant shunts were quantitatively confirmed. The diagnosis of complete shunt closure or absent shunt was correctly made in all 6 cases. RV EF reduction was found in 6 of 24 patients. LV EF reduction was also found in 6 of 24 patients. CONCLUSION: Flow measurements in Ao and Pu are more accurate than biventricular cine MRI for the assessment of Qp/Qs ratios. Flow measurements in Ao and Pu combined with biventricular cine MRI enables the quantification of hemodynamic significant shunts, higher grade VR and biventricular global systolic function with a single examination.

Adolescent↗

Tracing of the entorhinal-hippocampal pathway in vitro.

In vitro tract tracing allowing for continuous observation of the perforant path is a crucial prerequisite for experimental studies on the entorhinal-hippocampal interaction in an organotypic slice culture containing the entorhinal cortex, the perforant path, and the dentate gyrus (OEHSC). We prepared horizontal slices of the temporal entorhinal-hippocampal region of the rat on a vibratome, and the perforant path axons were traced by application of the fluorescent tracer Mini Ruby on the entorhinal cortex. After 2 days in vitro (div), the perforant path became visible in most cultures. Entorhinal neurons and single perforant fibers could be followed to the outer molecular layers of the dentate gyrus by in vitro fluorescence microscopy and it was possible to monitor the perforant path directly over a period of 25 div. Moreover, ultrastructural analysis proved the existence of traced perforant path boutons forming synapses with spines and dendritic shafts in the outer molecular layers of the dentate gyrus. Transsection of the prelabelled perforant path in vitro resulted in anterograde degeneration and subsequent phagocytosis of axonal material by activated microglial cells in the zone of denervation. In conclusion, in vitro tracing demonstrates the maintenance of the entorhinal-hippocampal pathway in OEHSCs and permits monitoring of dynamic changes in the prelabeled perforant path after various lesion paradigms, e.g., transsection or neurotoxin treatment. This approach permits further studies on the efficacy of neuroprotectants, cytokines, and growth factors in the treatment of lesion-induced neuronal degeneration.

Animals↗

Changes in perfusion pattern using ECD-SPECT indicate frontal lobe and cerebellar involvement in exercise-induced paroxysmal dystonia.

The clinical features of exercise-induced paroxysmal dystonia (EPD) are delineated in a pedigree including two affected members (both male) showing an autosomal-dominant inheritance trait. Gait analysis using kinematic electromyography during the motor attacks revealed coactivation of antagonistic calf muscles characteristic of dystonia. In the interval, impaired muscular alternation was observed. To characterize further the pathophysiological basis of the condition, ictal and interictal cerebral perfusion SPECT studies using technetium 99m-ethyl cysteinate dimer (ECD) were performed to establish whether cortical hyperactivity indicative of epilepsy is present during the motor attacks and to identify regional changes in the ictal perfusion pattern that could indicate an anatomic structure relevant to the disease. During the motor attacks, decreased ictal perfusion of the frontal cortex was found in both patients. In contrast, increased cerebellar perfusion was observed. The perfusion of the basal ganglia also decreased. No cortical hyperperfusion indicative of an epileptic nature was seen. Cerebellar hyperactivity in connection with prominent frontal hypoactivity has also been described in both the idiopathic and the symptomatic forms of dystonia. Our findings therefore suggest that EPD represents a paroxysmal movement disorder rather than epilepsy. It is concluded that changes in frontal and in cerebellar function are relevant to the pathophysiology of EPD.

Adolescent↗

[The fluoroscopy-guided implantation of subcutaneous venous ports: the complications and long-term results].

PURPOSE: Evaluation of technical success rate, long-term outcome and initial complication rate in patients with fluoroscopically guided port implantation. MATERIAL AND METHODS: Between January 1994 and April 1997 124 ports were implanted under fluoroscopic guidance in 120 patients. Indications for port implantation were anti-cancer chemotherapy, antibiotic and supportive therapy in patients with tumours or cachexia. RESULTS: Implantation was technically successful in 98.4% of the patients. We had a 3.2% minor complication rate that did not necessitate further treatment. One pneumothorax required a chest tube (0.8%). During a total of 17,534 days, complications occurred in 10.8% of all ports, 6.9% of the ports had to be explanted because of these complications. CONCLUSIONS: Insertion of ports under fluoroscopic guidance has a low complication rate and good long-term results. The rate of 93.1% of functioning ports is superior to that reported in other studies. It is less costly and has a lower complication rate than surgical implantation. Therefore it seems to be the method of choice for patients requiring long-term subcutaneous venous access for chemotherapy or supportive therapy in malignant tumours or other emaciating diseases.

Adult↗