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Biomedical subjects

G Becker

Publications and source records attributed to G Becker.

At least 163 records · Page 9Linked to original sources

Clusterin (Apo J) protects against in vitro amyloid-beta (1-40) neurotoxicity.

Clusterin is a secreted glycoprotein that is markedly induced in many disease states and after tissue injury. In the CNS, clusterin expression is elevated in neuropathological conditions such as Alzheimer's disease (AD), where it is found associated with amyloid-beta (A beta) plaques. Clusterin also coprecipitates with A beta from CSF, suggesting a physiological interaction with A beta. Given this interaction with A beta, the goal of this study was to determine whether clusterin could modulate A beta neurotoxicity. A mammalian recombinant source of human clusterin was obtained by stable transfection of hamster kidney fibroblasts with pADHC-9, a full-length human cDNA clone for clusterin. Recombinant clusterin obtained from this cell line, as well as a commercial source of native clusterin purified from serum, afforded dose-dependent neuroprotection against A beta (1-40) when tested in primary rat mixed hippocampal cultures. Clusterin afforded substoichiometric neuroprotection against several lots of A beta (1-40) but not against H2O2 or kainic acid excitotoxicity. These results suggest that the elevated expression of clusterin found in AD brain may have effects on subsequent amyloid-beta plaque pathology.

Amyloid beta-Peptides↗

Cerebrovascular reserve capacity in patients with occlusive cerebrovascular disease: assessment with dynamic susceptibility contrast-enhanced MR imaging and the acetazolamide stimulation test.

PURPOSE: To quantitatively assess cerebrovascular reserve capacity in patients with occlusive cerebrovascular disease. MATERIALS AND METHODS: In 21 symptomatic patients with occlusive cerebrovascular disease, magnetic resonance (MR) imaging was performed with a 1.5-T system. Before, during, and after a brief bolus injection of gadopentetate dimeglumine into the antecubital vain, a series of 32 rapid T2*-weighted gradient-echo images of two different sections were acquired simultaneously to measure the concentration-time-curves in the brain tissue and in the brain-feeding arteries. Principles of indicator dilution analysis were applied to compute regional cerebral blood flow (rCBF) and volume. Each patient underwent two examinations, the first before and the second after acetazolamide stimulation. RESULTS: In the asymptomatic hemisphere, a mean increase in rCBF value of 47.1% was observed after acetazolamide stimulation. In the affected areas of the symptomatic hemisphere, a statistically significantly reduced response to acetazolamide stimulation was found, indicating a severely compromised cerebrovascular reserve capacity. CONCLUSION: MR imaging with the described techniques provides quantitative information about the cerebrovascular reserve capacity in patients with occlusive cerebrovascular disease.

Acetazolamide↗

Lenticular nucleus lesion in idiopathic dystonia detected by transcranial sonography.

We report the transcranial sonography (TCS) findings of the basal ganglia in 86 patients with dystonic disorders including idiopathic dystonia (facial, cervical, upper limb, and generalized dystonia), drug-induced tardive dystonia, dopa-responsive dystonia, and kinesigenic dystonia. The TCS was focused on alterations of the lenticular, caudate, raphe nuclei, and the thalamus. Seventy-five percent of patient with idiopathic cervical and 83% of those with idiopathic upper limb dystonia had a hyperechogenic lesion of the middle segment of the lenticular nucleus on the side opposite to the clinical dystonic symptoms. The ipsilateral side was also affected in 20%. In facial dystonia, only one-third of the patients revealed lenticular nucleus lesions. The mean area of the lenticular nucleus lesion opposite to the clinically affected side was 30 mm2 in cervical dystonia, 17 mm2 in upper limb dystonia, and 7.5 mm2 in facial dystonia. These lenticular abnormalities were significantly more frequent (p < 0.001) and their areas were significantly greater (p < 0.001) compared with a control group of 50 patients afflicted with radiculopathy. There was a significant correlation of the severity of symptoms with the intensity of lenticular nucleus hyperechogenicity in patients with cervical and upper limb dystonia (p < 0.05). Increased caudate nucleus echogenicity was present in 20% of patients with cervical and upper limb dystonia, mostly contralateral to the clinically affected side and raphe abnormalities were present in 7% of all patients with idiopathic dystonia. In contrast, there were no abnormalities of the lenticular nucleus or thalamus in nonidiopathic dystonias. We conclude that idiopathic dystonia is associated with lesions in the basal ganglia, particularly the lenticular nucleus, that can be visualized by TCS. An alteration of the basal ganglia matrix may be the pathologic basis of idiopathic dystonia with secondary affliction of striatopallidothalamic pathways.

Adult↗

[Stereotaxic convergent-beam irradiation. Initial experiences with the SRS 200 system].

BACKGROUND: The system SRS 200 for the stereotactic convergent beam irradiation described in this paper has a stereotactic floor stand, which allows the high precision rotation of a secondary collimator around an isocenter. This system is used since 1991 at the University Hospital of Tübingen for the treatment of patients with solitary brain metastases, acoustic neurinomas and arteriovenous malformations. PATIENTS AND METHODS: The attainable accuracy of the mechanics and dosimetry was studied within the scope of extensive quality assurance measures during its installation and before each patients' irradiation. The individual treatment steps from radiotherapy planning to irradiation were evaluated by means of a specially developed head phantom. Since the installation of the SRS 200 a total of 50 patients (21 solitary brain metastases, 12 acoustic neurinomas, 17 arteriovenous malformations) has been treated with the system. RESULTS: With 0.3 mm +/- 0.2 mm an excellent accuracy of the target point transfer and isocenter stability during irradiation was attained. The difference between calculated dose and dosimetric control measurements was smaller than 3%. The physical accuracy, however, is limited by the imaging resolution (CT and digital subtraction angiography). Of the patients 15% with solitary brain metastases developed complete remission, 20% partial remission and with 50% no further neurological deterioration was observed. Imaging revealed for 88% of the patients a reduced uptake of contrast medium or a regression of the tumor size. Six patients with acoustic neurinoma had anacusis already before radiotherapy. Regarding the other patients in the follow-up, hearing improved in 1 patient, 1 patient showed hearing deterioration, and all other patients hearing remained constant. MR and CT imaging revealed in 10 patients with acoustic neurinoma a reduced uptake of contrast medium and in 1 patient a tumor diminution. From the patients with arteriovenous malformation only 4 have been followed for more than 2 years after treatment. Therefore, statements about the rate of obliteration are not possible yet. Concerning pretherapeutic symptoms (headache 22%, convulsion 28%, neurological deficits 11%) 8/17 (47%) of the arteriovenous malformation patients showed an improvement, in 8 patients clinical findings were unchanged and 1 patient showed neurological deterioration. CONCLUSION: The stereotactic system SRS 200 allows an excellent mechanical accuracy in the radiosurgery with linear accelerators.

Adolescent↗

Transcranial duplex-sonography in intracranial hemorrhage. Evaluation of transcranial duplex-sonography in the diagnosis of spontaneous and traumatic intracranial hemorrhage.

The aim of this prospective clinical study was to evaluate the potential of bedside transcranial color-coded duplex sonography (TDS) in the assessment of patients with acute intracranial hemorrhage and respective complications. 74 patients (35 with spontaneous and 27 with traumatic hemorrhage, 12 excluded due to insufficient insonability) underwent 152 TDS examinations. The results were compared to computer-tomography (CT) as well as conventional transcranial Doppler sonography (TcD). The size and localisation of intracerebral hemorrhages as detected in TDS coincided in 39/42 examinations with CT findings; in cases of traumatic intracranial extracerebral hematoma TDS correlated in all but one case (18/19). The TDS findings for the diameter of third and lateral ventricles (n = 126) as for midline-shift (n = 26) showed a good correlation (p < 0.0005) to CT-measurements. TDS appears to be a useful bedside, non-invasive tool in order to detect and exclude intracranial complications in patients with intracranial hemorrhages.

Cerebral Hemorrhage↗

Peripheral nerve extract effects on mesenchymal cells.

Several common congenital limb disorders are characterized by normal tissue differentiation but abnormal somatic growth. These include: idiopathic clubfoot, idiopathic leg length discrepancy, hemi-atrophy and hemi-hypertrophy. Both clinical and research studies have suggested that peripheral nerves may be important in regulating somatic growth of limb tissues. To investigate the hypothesis that peripheral nerves convey trophic substances to mesenchymal tissues that are involved in the regulation of growth, we developed an in vitro assay to assess the effect of fractions of peripheral nerve on myoblast and chondroblast growth and differentiation in a mammalian (rat) system. Whole rat sciatic nerve extract was fractionated by ammonium sulfate precipitation and by affinity chromatography. Concavalin A chromatography resolved whole nerve extract into a glycoprotein and a non-glycoprotein fraction. Serial ammonium sulfate precipitation yielded three pellet fractions designated as 35%, 70%, and 100% pellets; corresponding to ammonium sulfate concentrations of 0 to 35%, 35 to 70%, and 70 to 100% saturation, respectively. Dialyzed solutions of these pellets as well as the fractions from Concavalin A chromatography were assayed for biological activity in micromass cultures of rat limb bud mesenchyme, which allowed assessment of both myoblast and chondroblast stimulation. Stimulation of protein synthesis and myoblast proliferation (as measured by MF20 staining) occurred with both 70% and 100% ammonium sulfate fractions. Stimulation of chondroblasts (as measured by the number of alcian blue staining nodules) occurred with the 35% and 100% fractions. The glycoprotein fraction from the affinity chromatography stimulated protein synthesis and myoblast proliferation and inhibited chondroblast development. Stimulation of chondroblasts was seen with the non-glycoprotein fraction. No effect on protein synthesis, myoblast proliferation or chondroblast proliferation was found in cultures treated with rat transferrin (transferrin has been reported to stimulate myoblasts in avian culture systems).

Ammonium Sulfate↗

Reduced echogenicity of brainstem raphe specific to unipolar depression: a transcranial color-coded real-time sonography study.

Echogenicity of the brainstem raphe was assessed in patients with major depression, bipolar affective disorders, and schizophrenia and compared with healthy adults employing transcranial color-coded real-time sonography. Forty probands were enrolled in each group. A highly significant reduction in raphe echogenicity was detected only in patients suffering from major depression. Echogenicity of the raphe was independent of age or sex and did not correlate with severity of the depressive syndrome or patient state. These findings are suggestive of structural desintegration of the brainstem raphe in unipolar depression, an anatomical region assumed to be a biological focus in the pathogenesis of depressive syndromes.

Adult↗

Stereotactic convergent beam radiosurgery versus stereotactic conformation beam radiotherapy.

By means of preliminary results in the treatment of patients with acoustic neurinoma the achievable accuracies, dose distributions and time consumption of stereotactic LINAC-based convergent beam radiosurgery are compared to those achieved with fractionated stereotactic conformation beam radiotherapy. Characteristics of both techniques are described. With the Tübingen radiosurgery system a good adaptation of the dose distribution to spherical or oval target volumes with a steep dose gradient was achieved, whereas homogeneity and adaptation of the dose distribution to irregularly shaped targets were better with the Heidelberg conformation technique. The mechanical accuracy of the Tübingen floorstand system was 0.3 mm +/- 0.2 mm, and that of the Heidelberg mask fixation system < 1 mm. Both methods require similar total treatment times. Nine patients were treated by the Tübingen radiosurgery system. The results are compared with 12 patients treated by conformation radiotherapy in Heidelberg. In both patient groups no further tumour growth occurred. Four of 9 single dose treated patients developed side-effects, such as temporary trigeminal and facial paraesthesia hearing deterioration and oedema. In contrast, patients treated by fractionated radiotherapy showed no side-effects. Relating to the short follow-up the results indicate that single dose application has certain drawbacks for special indications. Further studies have to work out which method gives the best treatment results.

Adolescent↗

Unidirectional fluxes of short-chain fatty acids across segments of the large intestine in pig, sheep and pony compared with guinea pig.

Unidirectional fluxes of short-chain fatty acids across pig, sheep and pony caecum, proximal and distal colon were studied under short-circuit current conditions in Ussing chambers. Findings are compared with results from guinea pig. Marked species differences are apparent; highest mucosal-to-serosal fluxes of acetate, propionate and butyrate were seen in guinea pig, lower values in pig and smallest fluxes in sheep and pony. Segmental differences between caecum, proximal and distal colon exist mainly in guinea pig and are less developed in pig, sheep and pony. Inhibition of Na+/H+ exchange by amiloride added to the mucosal solution decreased the mucosal-to-serosal fluxes of short-chain fatty acids clearly in guinea pig caecum and proximal colon, and very little in distal colon. This effect was somewhat less pronounced in pig caecum and distal colon, in caecum and distal colon of sheep and caecum of the pony. In pig, sheep and pony proximal colon and pony distal colon no significant inhibition was observed. Inhibition of the K(+)-H+ ATPase by addition of ouabain to the mucosal solution diminished mucosal-to-serosal fluxes of short-chain fatty acids in the guinea pig distal colon extensively. No comparable inhibition was seen in any of the other segments in the animals studied.

Amiloride↗

Abdominal wall metastasis following percutaneous endoscopic gastrostomy.

Percutaneous endoscopic gastrostomy (PEG) has become a widely used method for nutritional support, particularly in patients with advanced head and neck carcinomas. Since the method is easy and widely established it is necessary to assess possible complications, even rare ones. In this paper we report on two patients with vaccination metastasis following PEG insertion. Both patients had advanced squamous cell carcinoma of the head and neck or the upper esophagus. In three patients previous bougienage was performed, because of considerable stenosis of the pharynx and/or esophagus. Fast-growing metastases were found at the site of PEG insertion, with and without involvement of the gastric wall. In neither case was abdominal wall metastasis the cause of death. There is a small but definite risk of tumor seeding into the abdominal wall after PEG insertion for obstructive malignant tumors. The clinical impact of this finding, however, is still undefined and needs further investigation.

Abdominal Muscles↗

Some methodological issues in neuroradiological research in psychiatry.

An outline is given of some of the methodological issues discussed in neuroradiological research on psychiatric illness. Strengths and shortcomings of magnetic resonance imaging (MRI) in depicting and quantifying brain structures are described. Temporal lobe anatomy and pathology are easily accessible to MRI, whereas limits on anatomical delineation hamper approaches to frontal lobe study. White matter hyperintense lesions are sensitively depicted by MRI, but specificity is limited. Distinction of vascular and primary degenerative dementia is considerably improved by CT and MRI analysis. Computed tomography (CT) and MRI have enhanced the understanding of treatable organic psychiatric disorders, e.g., normal pressure hydrocephalus. Subcortical and white matter pathology has been replicated in CT and MRI studies of late-onset psychiatric disorders, clinical overlap with cerebrovascular disease or neurodegeneration may be of import. Transcranial sonography findings of brainstem structural change specific to unipolar depression may contribute to the understanding of affective psychoses. Magnetic resonance spectroscopy and functional MRI are likely to stimulate psychiatric research in the future.

Brain↗

The gastrointestinal tract of the rock hyrax (Procavia habessinica). 2. Fluid flow, production of short chain fatty acids and absorption of water and electrolytes.

In the digestive tract of the rock hyrax (Procavia habessinica), water is absorbed from the small intestine and from the wider part of the connecting colon running between the caecum and the colonic sac. Only little water absorption occurs from these two fermenting chambers. The outflow from the caecum is much higher than from the colonic sac mainly due to the effective absorption in the connecting colon with its very large absorptive area. A significant lower osmolality was found in the caecal contents compared with the contents in the colonic sac. The Na/K ratio was 10.7 and 1.7, respectively in these sections. Short chain fatty acids are produced at a rate of nearly 10 mmol/100 ml/hr in the contents of both the caecum and the colonic sac. The results are discussed in relation to the findings in domestic and laboratory animals.

Animals↗

Preoperative and postoperative follow-up in high-grade gliomas: comparison of transcranial color-coded real-time sonography and computed tomography findings.

Twenty patients with high-grade gliomas were prospectively studied by pre- and postoperative transcranial color-coded real-time sonography (TCCS) and CT, to determine the sensitivity of TCCS in the identification of residual tumor and tumor regrowth. Each patient was subjected to preoperative and early postoperative CT (postoperative day 1) and TCCS examinations (postoperative days 6 to 8) and subsequent CT and TCCS follow-up examinations within a time interval of 6 weeks to 3 months. In eight patients, a total of 15 biopsy specimens were intraoperatively obtained from the wall of the resection cavity. Histological findings of intraoperative biopsy specimens showed that hyperechogenic areas adjacent to the resection cavity always contained residual tumor tissue. Early postoperative TCCS identified these hyperechogenic areas in 19 of 20 patients. In 12 patients, postoperative CT revealed contrast enhancement at the resection margin, indicating residual tumor. In these patients the extension of these hyperechogenic areas on TCCS exceeded the contrast-enhancing areas on CT by a mean of 58%. In eight patients, postoperative CT displayed no contrast enhancement along the border of resection. TCCS and histological findings indicated residual tumor in seven of these eight patients. The size of the hyperechogenic lesions identified by postoperative TCCS increased in time and follow-up examinations revealed that tumor regrowth arose from these hyperechogenic areas in all patients. In four patients, tumor regrowth was identified, on average 0.7 months earlier by TCCS than by CT. From these data we conclude that the sensitivity of TCCS in detection of residual tumor and tumor regrowth seems to be superior to CT. The value of TCCS requires further clarification by comparative studies including histology and MRI.

Biopsy↗

Transcranial color-coded real-time sonography of intracranial veins. Normal values of blood flow velocities and findings in superior sagittal sinus thrombosis.

Sonographic findings in patients with superior sagittal sinus thrombosis were compared to those in healthy adults. Two patients with angiographically verified superior sagittal sinus thrombosis were examined by transcranial color-coded real-time sonography (TCCS) after intravenous application of a pulmonary stable ultrasound contrast agent. For comparison, 10 patients without venous pathology had contrast-enhanced TCCS; in addition, 30 healthy adults had plain TCCS to determine the identification rate for deep and superficial venous segments and to define normal values of venous blood flow velocities. The straight sinus was identified in 22 of 30 healthy subjects by plain TCCS, and in 9 of 10 patients by contrast-enhanced TCCS. The mean peak and angle-corrected blood flow velocity was 19.1 +/- 7.1 cm/sec. The superior and inferior sagittal sinuses were identified by contrast-enhanced TCCS in 2 and 1 subjects, respectively; they were never seen on plain TCCS. In the 2 patients with sagittal sinus thrombosis a distinct increase of blood flow velocity was recorded from the straight sinus (83 and 92 cm/sec), most likely reflecting collateral circulation. These preliminary data indicate that TCCS and particularly contrast-enhanced TCCS permit identification and blood flow measurements within the deep and occasionally, the superficial venous system. TCCS may contribute to an assessment of hemodynamic repercussions of venous thrombosis and may indicate the risk of venous infarction and hemorrhage.

Adult↗

ELISA technique for quantification of surfactant protein B (SP-B) in bronchoalveolar lavage fluid.

Surfactant protein B (SP-B) is one of the essential constituents of the alveolar surfactant system, presenting mainly in the form of SP-B dimer. The measurement of this molecule in biologic samples has been hampered by its extreme hydrophobicity and intimate association with surfactant lipids. We developed a solid-phase, adsorption-based enzyme-linked immunosorbent assay (ELISA) technique for the quantification of SP-B in aqueous solutions. The ELISA employs the hydrophobicity of SP-B for direct binding of this compound to polystyrol immunosorbent plates. Samples are mixed with propanol (1:1 vol/vol) to achieve a homogeneous dispersion of their lipophilic constituents prior to adsorption to the wells. After fluid removal by evaporation, trifluoroethanol is added to optimize SP-B-polystyrol binding, and is then removed, again by evaporation. Subsequent washing procedures (diisopropyl-ether/butanol; Tween 20 in phosphate buffered saline [PBS]) selectively remove phospholipids. Solid phase-bound SP-B is detected by a monoclonal mouse antibody against porcine SP-B, cross-reacting with the apoprotein of human origin. For amplification, a biotinylated anti-mouse antibody and the avidin/biotin-peroxidase technique are used. Steep calibration curves with an excellent reproducibility are obtained for SP-B dimer (range: 0.3125 to 40 ng/well), either introduced directly into the immunosorbent-plate wells or previously admixed with synthetic phospholipid mixtures. SP-B monomer is detected with approximately 10% efficiency as compared with the dimer (wt/wt). Cross-reactivities with human SP-A and SP-C or albumin are negligible. Experiments with spiking of human bronchoalveolar lavage fluid (BAL) samples with different quantities of SP-B dimer revealed virtually complete apoprotein recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗