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Biomedical subjects

R Felix

Publications and source records attributed to R Felix.

At least 685 records · Page 38Linked to original sources

Microperfusion in coronary artery disease under treatment with the calcium antagonist gallopamil.

The calcium antagonistic principle, i.e. the inhibition of calcium influx into the heart muscle cell and smooth muscle cell, in this particular case gallopamil as an example of a drug with this principle of action, can certainly be regarded as one of the most important concepts in modern coronary therapy. On account of the increase of myocardial perfusion, which is ascribed to this calcium antagonist, gallopamil may be administered as an adjunct to postoperative therapy. It is even a drug alternative to bypass grafting. Previous investigations of the ST segment and subjective ischemic parameters have not always shown coherent findings. The purpose of this study was to objectify clinical improvement after therapy with gallopamil (Procorum) by means of reliable methods and reproducible measurements. Myocardial perfusion was analysed in 31 patients by longitudinal tomoscintigraphy before and after therapy with 2 x 2 mg gallopamil intravenously and 6 weeks at 3 x 50 mg/d orally followed by placebo control. The computerized circumferential mapping of impulse rates showed a significant increase of impulse density in ischemic segments after both intravenous and oral therapy with gallopamil.

Administration, Oral↗

Fatty acid oxidation in bone tissue and bone cells in culture. Characterization and hormonal influences.

Fatty acid oxidation and its hormonal modulation were investigated in cultured rat calvaria and in cultivated cell populations. The latter were obtained from calvaria of newborn rats by sequential time-dependent digestion with collagenase, yielding eight cell populations: the early ones containing mainly fibroblasts, the middle ones being osteoblast-like, and late ones osteoblast-osteocyte-like. In calvaria, fatty acid oxidation was increased by adding 0.1 mM- and 1.0 mM-palmitate to the medium, containing 10% (v/v) fetal-calf serum. No effect was found after parathyrin addition in vitro or when injected in vivo. All cell populations obtained by sequential digestion were found to oxidize palmitate, whereby the osteoblast-like cells showed a lower oxidation rate than the other populations. Both parathyrin and calcitonin had no effect on fatty acid oxidation. 1,25-Dihydroxycholecalciferol at 1-100 nM and 24,25-dihydroxycholecalciferol at 100 nM increased oxidation primarily in the population enriched with osteoblast-like cells. Insulin at 1.6 microM diminished it in the cell populations enriched with osteoblast-like cells and in the late bone-cell fraction. However, glucagon had no effect. The energy provided by fatty acid oxidation in this system is approx. 40-80% of glucose metabolism, suggesting that this event may be of importance in the energy metabolism of bone.

Adenosine Triphosphate↗

Use of nuclear magnetic resonance imaging to show regression of hypertrophy with ramipril treatment.

Thirty-two patients with arterial hypertension (diastolic blood pressure greater than 95 mm Hg) were treated with ramipril for 3 months. The aim of the study was to achieve an effective decrease in blood pressure and demonstrate reliably and reproducibly that regression of left ventricular hypertrophy takes place with ramipril treatment. Nuclear magnetic resonance images and echocardiographic measurements of the left ventricle were therefore made before treatment started, 4 hours after the first dose, 14 days after the start of treatment and after 3 months of treatment. The thickness of the septum decreased from 19.57 to 15.20 mm on magnetic resonance scans and from 18.78 to 14.57 mm on echocardiograms. The values were reproduced 3 times at the same measuring point and means were calculated. The septum and posterior wall of the left ventricle were also measured at 3 different points. With negligible scatter, the values obtained were reproducible and the differences were highly significant (p = 0.001). A parallel decrease in blood pressure to levels 15% below baseline was also observed. The therapeutic aim of achieving diastolic blood pressure levels of less than or equal to 90 mm Hg was achieved in all patients. In addition to reducing the blood pressure significantly, the angiotensin converting enzyme inhibitor ramipril caused a significant regression of pathologic left ventricular hypertrophy, which was demonstrated clearly using magnetic resonance imaging and echocardiography.

Angiotensin-Converting Enzyme Inhibitors↗

Cell-specific processing of preprosomatostatin in cultured neuroendocrine cells.

We have previously found that preprosomatostatin is processed accurately to both somatostatin-14 and somatostatin-28 in pituitary gonadotrophs of transgenic mice. The foreign somatostatin peptides have been shown to enter the regulated secretory pathway of these cells. To determine whether accurate preprosomatostatin processing can occur in any neuroendocrine cell, we introduced preprosomatostatin cDNA expression vectors into several different neuroendocrine cell lines. We found that prosomatostatin was cleaved efficiently to somatostatin-14 and somatostatin-28 in RIN 5F and AtT20 cells, but not in GH4 or PC12 cells. The ability of a particular cell type to process prosomatostatin did not correlate with cellular storage capacity and was independent of the level of biosynthesis of the precursor. These data suggest that prosomatostatin processing requires specific pathways which are present in some neuroendocrine cells, but not in others.

Adrenal Gland Neoplasms↗

Effect of bisphosphonates on proliferation and viability of mouse bone marrow-derived macrophages.

Bisphosphonates (BP) are powerful inhibitors of bone resorption. Their mechanism of action, although still unclear, is now believed to be at the cellular level. In this study we investigated the effects of these compounds on proliferation, induced either by L-cell conditioned medium (CSF-1) or 4-phorbol 12-myristate 13-acetate (PMA) of bone marrow cells (BMC) and on CSF-1-induced proliferation and viability of bone marrow derived macrophages (BMDM phi). BMC proliferation, measured by [3H]-TdR incorporation or by clonal assay in soft agar, was significantly inhibited by 4-amino-1-hydroxybutylidene-1,1-bisphosphonate (AHBuBP) and 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (AHPrBP) at 2.5 x 10(-7) M and by dichloromethylenebisphosphonate (Cl2MBP) at 2.5 x 10(-6) M. This inhibitory effect was also confirmed on the proliferation, measured by [3H]-TdR incorporation, of BMDM phi. In the absence of CSF-1, the viability of this latter cell population, estimated by DNA content per well and lactate dehydrogenase (LDH) released into the medium, was affected in the following order of concentrations: Cl2MBP, 1.0 x 10(-4) M; AHBuBP, 5.0 x 10(-5) M; and AHPrBP, 2.5 x 10(-5) M. Since osteoclasts and macrophages might share a common early progenitor cell, probably under the control of CSF-1, the effect exerted by BP on the proliferation of the macrophage precursors may also be extended to the osteoclast precursors.

Animals↗

Fluoroimmunoassay: an alternative to radioimmunoassay?

Fluoroimmunoassays appear to be an alternative to conventional radioimmunoassays and immunoradiometric assays because of the high specific activity of their label, thus promising high sensitivity and excellent precision. According to IFCC recommendations for the assessment of new laboratory methods, we evaluated precision, accuracy, linearity, lower detection limit and normal reference ranges of commercially available immunofluorometric assays of alpha-fetoprotein, choriongonadotropin and thyrotropin. In addition, thyrotropin content in sera of 147 patients was measured by immunofluorometric assay. Analysis of immunofluorometric assays gained performance data comparable to those of currently used immunoradiometric assays. Regression studies performed against currently employed methods showed accuracy of all three immunofluorometric assays. Results of immunofluorometric assay for thyrotropin demonstrated that sera of hyperthyroid subjects were distinguished from those of euthyroid subjects from basal thyrotropin alone. We conclude that immunofluorometric assays are an alternative to immunoradiometric assays which anybody concerned about the future of in vitro nuclear medicine should be aware of.

Chorionic Gonadotropin↗

Murine osteoblastlike cells and the osteogenic cell MC3T3-E1 release a macrophage colony-stimulating activity in culture.

The osteoclast may be of hematopoietic lineage and as such its development could be regulated by colony-stimulating factors. Since there is much interest as to whether osteoblasts influence bone resorption, we examined whether bone cells produce colony-stimulating activity. Both cells isolated from neonatal calvaria and the osteogenic cell MC3T3-E1 were found to constitutively release a colony-stimulating activity possessing characteristics of a macrophage colony-stimulating factor, as determined by basic biochemical purification and by identity of colonies induced in cultures of bone marrow cells. Release could be increased by the presence of the bone-resorbing agents lipopolysaccharide and 1,25 dihydroxyvitamin D3. We conclude that the osteoblast may contribute to both the processes of osteoclast formation and of hematopoiesis through the secretion of colony-stimulating activity into the adjacent bone marrow.

Animals↗

Transforming growth factor-beta reduces the phenotypic expression of osteoblastic MC3T3-E1 cells in monolayer culture.

Transforming growth factor beta (TGF-beta) regulates cell growth and differentiation. Since it is abundant in bone, we have studied the effect of the polypeptide upon the growth and phenotypic expression of murine osteoblastic cells in monolayer culture. Its actions were compared to those of epidermal growth factor (EGF), another hormonally active polypeptide known to alter bone cell function. Picogram amounts of TGF-beta were found to inhibit the growth and phenotype (alkaline phosphatase and cAMP response to parathyroid hormone) of the clonal nontransformed MC3T3-E1 osteoblastic cell line. EGF also inhibited phenotypic expression, although at higher (nanogram) concentrations, but stimulated cell growth. The low concentration of TGF-beta required to inhibit growth and phenotype of osteoblastic cells together with its abundance in bone suggest that TGF-beta may be an important regulator of bone cell function.

Alkaline Phosphatase↗

[Characteristics of intracranial meningioma imaged by magnetic resonance tomography].

Twenty-three patients with intra cranial meningiomas were examined by means of magnetic resonance tomography (MRT). In 13 patients the paramagnetic contrast medium gadolinium DTPA was used. Meningiomas show only slight changes in signal intensity compared with brain in the spin-echo mode, the greatest contrast being found on photon density images (TR 1600 ms, TE 35 ms). In T1 images, more than 50% patients showed a low signal margin between tumour and brain, Hyperostosis of the calvarium is easily recognised, but MRT is unreliable for showing tumour calcification. After intravenous injection of gadolinium DTPA, there was marked homogeneous uptake in the meningiomas. These signs are useful for the diagnosis of a meningioma by MRT.

Adult↗

[Rapid nuclear magnetic resonance tomography. Initial results of studies using the new gradient echo sequence].

In 60 patients with intracerebral lesions, examined by MRI, a new gradient-echo sequence was employed. This imaging technique uses excitation pulse angles smaller than 90 degrees and echoes are produced by an inversion of the read gradient. Since no 180 degrees pulse between successive excitations is necessary, very short repetition times can be used. Depending on matrix-size and signal averaging, MR imaging time can be reduced to approximately 5 to 40 seconds for single slice scan. For comparison, conventional T1- and T2-weighted spin-echo images were performed. Diagnostic results of the T1-weighted fast gradient-echo images corresponded with T1-weighted spin-echo images in 30% of cases. Diagnostic information was lower in 40% of cases. In the remainder of cases (30%) lesions were not detected with the gradient-echo technique. This especially applied to multiple sclerosis, infarctions and low-grade gliomas. Due to image artefacts and low contrast, visualization of small pathologic lesions was limited. Significant improvement of tumor visualization on gradient-echo scans was observed after injection of Gd-DTPA (0.1 mmol/kg).

Brain Diseases↗

[Magnetic resonance tomography of ovarian tumors].

The results of 64 MR examinations in 52 patients with benign, malignant and inflammatory lesions of the adnexa are presented. In each case, surgery or laparoscopy was carried out, so that it was possible to compare the findings on MRT with the histological results. Multiplanar images of gynaecological lesions provide excellent demonstration of the pathological anatomy. High soft tissue contrast makes it possible to differentiate tissues, particularly in the case of serous, mucinous and haemorrhagic fluid collections, as well as solid and fat-containing tissue. High sensitivity may be expected in the demonstration of dermoid and endometrial cysts. The distinction between benign and malignant lesions must, however, be based on morphological criteria. The combination of T1 and T2 sequences is necessary for adequate MR examinations of gynaecological lesions.

Adnexa Uteri↗

[Imaging diagnosis of ovarian tumors. Magnetic resonance tomography in comparison with computerized tomography and sonography].

The present paper compares the results of MRT with sonography in 64 patients with tumours of the adnexa in 35 patients examined by CT. There was no difference between these three imaging methods as regards lateralisation of the lesion. MRT provided better differentiation because of the excellent demonstration of the uterus and of tumours of the adnexa. Detailed tissue characterisation, particularly as regards cystic lesions, provides improved diagnostic information. MRT has problems, however, because of its low spatial resolution and the difficulty in differentiation from bowel loops. At present sonography and CT is better at establishing a differential diagnosis. CT remains the method of choice for tumour staging.

Adolescent↗

[Magnetic resonance tomography of intrathoracic tumors].

65 patients suspected of having intrathoracic masses were studied using magnetic resonance imaging (MRI) and computed tomography (CT). The intensity difference between mass and adjacent normal tissue or mediastinal fat was greater on MRI than on CT images. MRI was superior to CT in differentiating bronchogenic carcinomatous tumours from postobstructive pneumonia and/or lobar collapse. MRI images most clearly depicted obstructed mediastinal vessels and were also able to indicate intravenous flow reductions. The latter could be demonstrated by an increase of signal intensity within venous structures proximal to the obstruction. In patients with lung cancer no significant differences were found between the two imaging methods for the evaluation of tumour extent or node involvement.

Bronchogenic Cyst↗

[Oral contrast medium for magnetic resonance tomography of the abdomen. II. Phase I clinical testing of gadolinium-DTPA].

20 male volunteers were examined by MRI to determine safety and efficacy of Gd-DTPA formulations for gastrointestinal (GI)-tract contrast enhancement. Prior to and after administration of contrast spin-echo images were obtained. Volunteers were studied after administration of 10 ml contrast medium/kg (1.0 mmol Gd-DTPA/l vs. 0.5 mmol Gd-DTPA/l, no mannitol vs. 15 g mannitol/l vs. 30 g mannitol/l). Gd-DTPA provided high signal intensity in the GI tract. Contrast medium in gastric lumen and duodenum permitted improved delineation of pancreatic head and ventral outline in 16 of 20 subjects. No clinically relevant side effects were seen.

Abdomen↗

Conventional and rapid MR imaging of the liver with Gd-DTPA.

Twenty-three patients with malignant hepatic tumors underwent magnetic resonance (MR) imaging before and after intravenous administration of gadolinium-diethylene-triaminepentaacetic acid (DTPA). Two different doses were used, 0.1 mmol/kg and 0.2 mmol/kg. The larger dose proved to be more effective than the smaller dose. The signal-enhancement-to-noise ratio was significantly larger in the tumor than in the liver (2 alpha less than or equal to .05). In a moderately T1-weighted spin echo (SE) sequence (SE 400/30) (repetition time [TR] msec/echo time [TE] msec), the tumor was better defined 6 minutes after administration of Gd-DTPA. More strongly T1-weighted sequences--that is, SE 200/20 and inversion recovery 1,500/35/400 (TR msec/TE msec/inversion time, msec)--showed significantly worse contrast between tumor and liver (signal-difference-to-noise ratio [SD/N]) 10 and 15 minutes after administration (2 alpha less than or equal to .05). On the other hand, the low SD/N in the rapid MR imaging sequence was significantly improved (2 alpha less than or equal to .05). The most important indications for administration of Gd-DTPA in diagnosing hepatic tumors are the presentation of perfusion conditions and contrast optimization in rapid MR images.

Adult↗

Temporal-lobe epilepsy: comparison of CT and MR imaging.

In 50 patients with temporal-lobe epilepsy, CT and MR findings were compared. Axial CT scans were obtained before and after administration of contrast material. Coronal MR imaging was carried out with two spin-echo (SE) sequences with a repetition time of 1600 msec and echo times of 35 or 70 msec (SE 1600/35, SE 1600/70). A focal lesion was detected by CT in 12 cases and by MR in 16 cases. If discrete attenuation or signal abnormalities are also taken into account, CT provided a positive finding in 13 cases and MR imaging in 20 cases. With the exception of a small calcification, all the lesions revealed on the CT scans were also detected on the MR images. Among the examinations assessable for temporal-lobe asymmetry, signs of a unilateral reduction in temporal-lobe size were seen on two of 35 CT scans and on 15 of 38 MR images. In three patients who had temporal-lobe resection, a subsequent comparison was made between CT, MR imaging, and pathology. Histologically proven glial reactions that could not be detected on CT were demonstrated as high-signal-intensity lesions on the SE 1600/70 image. We conclude that MR scanning, with its higher sensitivity, superior image quality, and ability of multiplanar imaging, should be the imaging technique of choice in the diagnosis of temporal-lobe epilepsy.

Adolescent↗