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Biomedical subjects

A Müller

Publications and source records attributed to A Müller.

At least 253 records · Page 14Linked to original sources
PubMed1998

Relationship between disease activity and serum levels of vitamin D metabolites and PTH in rheumatoid arthritis.

In several studies on patients with rheumatoid arthritis, an association of bone loss with a persistently high disease activity has been found. The aim of our study was to investigate the relation between disease activity and serum levels of vitamin D metabolites, parathyroid hormone (PTH), and parameters of bone turnover in patients with rheumatoid arthritis. A total of 96 patients (83 women and 13 men) were divided into three groups according to disease activity measured by serum levels of C-reactive protein (CRP). In the whole group, serum levels of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) (P < 0.001) and PTH (P < 0.05) were negatively correlated to disease activity. The urinary excretion of collagen crosslinks--pyridinoline (Pyd) (P < 0.001) and deoxypyridinoline (Dpd) (P < 0.05)--showed a positive correlation with disease activity. The inverse correlation between serum 1,25(OH)2D3 and disease activity was separately evident in patients with (P < 0.001) and without (P < 0.01) glucocorticoid treatment, in pre- (P < 0.01) and postmenopausal (P < 0.001) women, and in men (P < 0.01). 1,25(OH)2D3 and PTH serum levels were positively correlated to serum bone alkaline phosphatase (ALP) (P < 0.01). The results indicate that high disease activity in patients with rheumatoid arthritis is associated with an alteration in vitamin D metabolism and increased bone resorption. The decrease of 1,25(OH)2D3 levels in these patients may contribute to a negative calcium balance and inhibition of bone formation. Furthermore, low levels of 1,25(OH)2D3 as an endogenous immunomodulator suppressing activated T cells and the proliferation of cells may accelerate the arthritic process in rheumatoid arthritis.

Adolescent↗
PubMed1998

The ependyma in chronic hydrocephalus.

H-Tx rats produce congenitally hydrocephalic offspring with varying severity of the condition. We used moderately hydrocephalic rats without evident clinical signs of hydrocephalus and normal controls from the same stock when they were at least 1.5 years old. Macroscopic anatomy was studied by MRI and in fixed brain slices and the ultrastructure of the ependyma, with REM. Apart from markedly stretched areas, where the ependyma was totally destroyed and subependymal structures directly exposed to the CSF, the density of ependymal microvilli and of tufts of cilia was reduced in proportion to the ventricular distension of a given area. A supraependymal "network"--never seen before in acute hydrocephalus--was found, whose purpose is probably to prevent further ventricular enlargement. We conclude that even in arrested hydrocephalus the ependymal sequelae of hydrocephalus are similar to those of the acute stage, illustrating the extremely limited potential for recovery, but the organism seems nevertheless to react with an internal stabilization of the ventricular system.

Animals↗
PubMed1998

Collagen cross-links in fibromyalgia syndrome.

OBJECTIVE: The acceptance of fibromyalgia as a disease entity and its definitive diagnosis have been hampered by a dearth of knowledge concerning the underlying pathophysiology of this disease and the lack of specific biochemical markers applicable to its diagnosis. To determine whether abnormal collagen metabolism is a characteristic of fibromyalgia, we have analyzed collagen metabolites in the urine and serum of patients with fibromyalgia. METHODS: The diagnosis of fibromyalgia was made according to the American College of Rheumatology criteria. Urine and serum were collected under standardized conditions from 39 patients and 55 age- and sex-matched controls. Pyridinoline (Pyd) and deoxypyridinoline (Dpyd), which represent products of lysyl oxidase-mediated cross-linking in collagen and are indicators of connective tissue and bone degradation, respectively, were analyzed by ion-paired and gradient HPLC method with fluorescence detection (HPLC). Levels of hydroxypyroline (Hyp), a collagen turnover marker, were also measured. The findings were related to creatinine levels and the Pyd/Dpyd ratio determined. RESULTS: The Pyd/Dpyd ratios in the urine and serum and the Hyp in the urine were significantly lower in patients with fibromyalgia than in healthy controls. CONCLUSION: Decreased levels of collagen cross-linking may contribute to remodeling of the extracellular matrix and collagen deposition around the nerve fibers in fibromyalgia and contribute to the lower pain threshold at the tender points. Analysis of altered collagen metabolism either by histologic examination on biopsy or, preferably, by HPLC analysis of collagen metabolites in urine or serum may aid to understand more about the pathogenesis of fibromyalgia.

Amino Acids↗
PubMed1998

Incidence of post-lumbar puncture syndrome reduced by reinserting the stylet: a randomized prospective study of 600 patients.

The post-lumbar puncture syndrome (PLPS) can best be explained by prolonged spinal fluid leakage owing to delayed closure of a dural defect. Its incidence after spinal anaesthesia is much lower than after diagnostic lumbar puncture (LP). This difference could be caused by a strand of arachnoid, which might enter the needle with the outflowing cerebrospinal fluid (CSF) during diagnostic LP and upon removal of the needle be threaded back through the dura to produce prolonged CSF leakage. To find a technique that further reduces the incidence of PLPS, this hypothesis was tested by evaluating the effect that reinserting the stylet before removing the needle had on the incidence of PLPS. By reinserting the stylet to the tip of the needle, the hypothesized strand would be pushed out, thereby reducing the frequency of PLPS. Sprotte's "atraumatic needle" (21 gauge) was used for LP. A total of 600 patients participated in the prospective study. They were randomized into two groups and questioned about their complaints every day for up to 7 days after the LP. All LPs were performed by two experienced neurologists (T.B., M.S.). In 300 patients, the stylet was reinserted to the tip of the eedle; in the other 300 it was not reinserted. Whereas 49 of the 300 patients without reinsertion developed PLPS, only 15 of the 300 patients with reinsertion did. This significant difference (16.3 vs 5.0%, P < 0.005, chi square test) supports our hypothesis. On the basis of our results, we recommend reinserting the stylet before removing the needle in order to reduce the incidence of PLPS.

Adult↗
PubMed1998

Indole-3-acetic acid is synthesized from L-tryptophan in roots of Arabidopsis thaliana.

The promoter of the nit1 gene, encoding the predominantly expressed isoform of the Arabidopsis thaliana (L.) Heynh. nitrilase isoenzyme family, fused to the beta-glucuronidase gene (uidA) drives beta-glucuronidase expression in the root system of transgenic A. thaliana and tobacco plants. This expression pattern was shown to be controlled developmentally, suggesting that the early differentiation zone of root tips and the tissue surrounding the zone of lateral root primordia formation may constitute sites of auxin biosynthesis in plants. The root system of A. thaliana was shown to express functional nitrilase enzyme. When sterile roots were fed [2H]5-L-tryptophan, they converted this precursor to [2H]5-indole-3-acetonitrile and [2H]5-indole-3-acetic acid. This latter metabolite was further metabolized into base-labile conjugates which were the predominant form of [2H]5-indole-3-acetic acid extracted from roots. When [1-13C]-indole-3-acetonitrile was fed to sterile roots, it was converted to [1-13C]-indole-3-acetic acid which was further converted to conjugates. The results prove that the A. thaliana root system is an autonomous site of indole-3-acetic acid biosynthesis from L-tryptophan.

Aminohydrolases↗
PubMed1998

Quantitation of the octadecanoid 12-oxo-phytodienoic acid, a signalling compound in plant mechanotransduction.

The octadecanoid 12-oxo-phytodienoic acid (OPDA) is an intermediate in biosynthesis of jasmonic acid in plants. A technique for the quantitation of this compound is described which has a limit of detection of 20 pg cis-OPDA corresponding to 4 ng g-1 tissue for the overall procedure and which uses high isotopic abundance [2H5]cis-(+/-)-OPDA, synthesized enzymatically by recombinant allene oxide synthase, as internal standard. The levels of cis-OPDA have been determined in a wide variety of monocotyledonous and dicotyledonous angiosperms and were found to vary considerably among different species. In mechanically stimulated tendrils of Bryonia dioica, the level of cis-OPDA increases several-fold, correlating with the initiation and progression of the free coiling response. In Phaseolus vulgaris internodes undergoing a thigmomorphogenic response, the levels of cis-OPDA were also found to increase several-fold well before the development of thigmomorphogenic symptoms. The thigmomorphogenic reaction could also be triggered by application of the octadecanoid structural analog, coronatine. Coronatine did not induce OPDA accumulation in treated tissues and is thus active per se. In both species, Bryonia dioica and Phaseolus vulgaris, the (+)-enantiomer of cis-OPDA is found and accumulates after mechanical stimulation. Our results establish 12-oxo-phytodienoic acid as a signalling compound in higher plant mechanotransduction.

Deuterium↗
PubMed1998

Resting metabolic rate in preadolescent girls at high risk of obesity.

OBJECTIVE: To investigate whether children at high risk of obesity have a reduced resting metabolic rate (RMR). DESIGN: Cross-sectional study. SUBJECTS: 93 healthy girls (age: 8-12 y) were allocated to one of four groups, according to the subjects' and their parents' weight status: group 1, overweight children with both parents overweight (OB/OB2; n = 17); group 2, normal weight children with both parents overweight (N/OB2; n = 28); group 3, overweight children of discordant parents (OB/OB1; n = 21) and group 4, normal weight children with both parents normal weight (N/OB0; n = 27). MEASUREMENTS: Weight, height, fat-free mass (FFM) and fat mass (FM) by bioelectrical impedance analysis (BIA), RMR (indirect calorimetry) for the duration of 25 min. RESULTS: Controlling for disparities in body composition, age and physical maturity, significant differences were found in adjusted group means of RMR (OB/OB2 1181 kcal/d; N/OB2 1276 kcal/d; OB/OB1 1234 kcal/d; N/OB0 1199 kcal/d; P < 0.02) with the OB/OB2 girls showing the lowest energy expenditure. CONCLUSION: We found evidence that preadolescent girls at risk of obesity, are not generally predisposed to a higher body weight, because of a greater metabolic efficiency. In fact, our data show that more emphasis should be laid on defining different subgroups of both overweight and normal weight subjects in studies investigating metabolic rate.

Aging↗
PubMed1998

Mutation of cis-proline 207 in mitochondrial creatine kinase to alanine leads to increased acid stability.

We show that the mutation of an uncharged residue far from the active site to another uncharged residue can have effects on the active site without disturbing the overall structure of the protein. Cis-proline 207 of mitochondrial creatine kinase was mutated to alanine. The mutant showed a decrease in the pH-optimum for ATP synthesis by 1.5 units while the maximum relative activity was lowered to 53% of the wild-type enzyme. In the direction of ATP consumption, the pH optimum was lowered by 1.3 units and the maximum relative activity was 49% of the wild-type enzyme. The enzyme kinetic parameters Km and Kd for the substrates did not change dramatically, indicating a largely unperturbed active site. Small-angle X-ray scattering was used to investigate the structural change concomitant with the mutation, yielding a scattering profile only slightly different from that of the wild-type enzyme. Neither the radius of gyration nor the molecular mass showed any significant differences, leading to the conclusion that quarternary organization and fold of the mutant and the wild-type enzymes were similar. Theoretical analysis suggests the most probable primary source of structural change to be a transition of residue 207 peptide bond torsional angle co from the cis to the trans configuration.

Creatine Kinase↗
PubMed1998

Percutaneous computed tomographic-controlled ventriculostomy in severe traumatic brain injury.

OBJECTIVE: Percutaneous computed tomographic (CT)-controlled ventriculostomy (PCV) was introduced for the monitoring of intracranial pressure in patients with severe traumatic brain injury who did not require simultaneous decompressive trepanation. METHODS: PCV (n = 14) was compared with conventional burr hole ventriculostomy (n = 13) based on prospectively collected data. RESULTS: PCV proved to be a successful technique in all cases and also when a burr hole ventriculostomy was impossible previously. There were no complications. In burr hole ventriculostomy, there were one unsuccessful insertion and one catheter contamination. The main advantage of PCV over burr hole ventriculostomy was a significant (p < 0.05) reduction in the time required to perform the procedure. In ventriculostomy directly after the initial evaluation in the emergency department, the operation time was reduced from 45 +/- 11 to 22 +/- 14 minutes. The interval between cranial computed tomography and start of operation was reduced from 78 +/- 38 to 33 +/- 12 minutes, and between initial cranial computed tomography and intensive care unit admittance, from 138 +/- 37 to 73 +/- 28 minutes. For patients requiring ventriculostomy while being treated in the intensive care unit, the duration of the procedure (i.e., absence from the intensive care unit) was able to be reduced from 111 +/- 24 to 81 +/- 21 minutes. CONCLUSION: Distinct time savings are the major advantages of PCV, allowing exact catheter positioning even with very narrow ventricles.

Adolescent↗
PubMed1998

A paramedian tangential approach to lumbosacral extraforaminal disc herniations.

OBJECTIVE: Extraforaminal disc herniations today are operated on via the so-called lateral approach. Clinical experience has shown that in contrast to levels L2/3-L4/5, this approach may become extremely difficult at the L5-S1 level. According to new microanatomic studies, the previous lateral approaches at this level often do not allow access to the neuroforamen without partial or total destruction of the L5-S1 facet joint. Postoperatively, this may lead to joint irritation with consecutive low back and pseudoradicular pain. To preserve the facet joint, a new approach was developed based on an anatomic study. METHODS: The approach was first considered with the help of bone specimens including ilium, vertebra 5, and sacrum. Thereafter, lumbar maceration specimens were prepared leaving ligaments, intervertebral discs, and joints intact. From these specimens, bony and ligamentous landmarks were deduced. Finally, the approach was tested on seven cadavers. Subsequently, the approach was performed on 13 patients and the intraoperative findings, the clinical feasibility, and the postoperative results were analyzed. APPROACH: After a transverse skin incision above the dorsal curvature of the ilium, the paravertebral muscles are dissected from the ilium medially toward the spinous process. Lateral from the apophyseal joint, a canal is drilled through the spongiosa of the sacrum. Primarily, a thin layer of inner cortex is spared to protect the content of the neuroforamen. Subsequently, it can easily be removed with the dissector to enter the extraforaminal space. In the depth of the drilled canal, the nerve root is found, because it is fixed at the sacrum near the disc space by the anterior lumbosacral ligaments. Riding on the nerve root, the intertransverse ligament and muscle can be removed with the punch. It is then possible to see the neuroforamen and extraforaminal space in front of the joint. Free fragments and contained discs can then easily be found and removed. CONCLUSION: Using this new approach, the L5-S1 joint remains intact. Space for instrumental manipulations is created in areas not essential for joint function. For this procedure, newly defined anatomic landmarks, such as the ileolumbar ligament, upper edge of the sacrum, lateral rim of the apophyseal joint, and para-articular notch, guide the operative route. In accordance with the preliminary anatomic studies, this approach was successfully used in 13 patients, and we think that it is a promising alternative that helps to preserve joint function and dorsal root ganglion integrity.

Adult↗
PubMed1998

Coronary artery stent placement with postprocedural antiplatelet therapy in acute myocardial infarction.

BACKGROUND: We have shown that coronary artery stent implantation in acute myocardial infarction (AMI) is feasible and safe when combined with effective postprocedural antiplatelet therapy. However, the concept of coronary stenting in AMI has not been validated in large cohorts. In this observational study, we investigated the outcome in 318 consecutive patients. METHODS AND RESULTS: From January 1995 until December 1996, 420 of 455 (92.3%) patients admitted to our institutions with AMI underwent infarct artery stent placement. This report describes the 318 patients treated with combined antiplatelet therapy whose AMI was not complicated by cardiogenic shock or mechanical ventilation before the intervention. Postinterventional therapy consisted of 100 mg aspirin and 250 mg ticlopidine twice daily. There were 21 (6.6%) cardiac events during 30-day follow-up: five cardiac deaths (1.6%), four nonfatal re-infarctions (1.3%) and 13 target vessel revascularizations (4.1%). Six months of clinical follow-up yielded a 94.7% survival rate free of repeat AMI. The rate of repeat interventions was 11%. Quantitative computerized angiography at 6 months, performed in 79.4% of the eligible patients, revealed a binary restenosis rate of 25%. CONCLUSIONS: With postprocedural antiplatelet therapy, coronary stenting in AMI yields favorable short- and long-term outcomes.

Angioplasty, Balloon, Coronary↗
PubMed1998

Extracellular ATP and bradykinin increase cGMP in vascular endothelial cells via activation of PKC.

Vasodilation by agents such as bradykinin and ATP is dependent on nitric oxide, the endothelium-dependent relaxing factor (EDRF). The release of EDRF results in elevation of cGMP in endothelial and smooth muscle cells (9). The signaling pathway that leads to increases in cGMP is not completely understood. The role of protein kinase C (PKC) in the elevation of cGMP induced by ATP and bradykinin was studied in cultured porcine aortic endothelial cells, by measuring PKC phosphorylation of a substrate and by measuring cGMP levels by radioimmunoassay. Extracellular ATP and bradykinin simultaneously elevated cGMP levels and PKC activity. The PKC inhibitors staurosporine, calphostin C, and Cremophor EL (T. Tamaoki and H. Nakano. Bio/Technology 8: 732-735, 1990; F. K. Zhao, L. F. Chuang, M. Israel, and R. Y. Chuang. Biochem. Biophys. Res. Commun. 159: 1359-1367, 1989) prevented the elevation of cGMP elicited by ATP and reduced that produced by bradykinin. Cremophor did not affect the elevation of cGMP by nitroprusside, an agent that directly increases guanylate cyclase activity (9). The PKC activator phorbol 12-myristate 13-acetate, but not a phorbol ester analog inactive on PKC, also elevated cGMP levels. These results suggest that EDRF agonists elevate cGMP in endothelial cells via PKC stimulation.

Adenosine Triphosphate↗
PubMed1998

Heterogeneous dopamine D2 receptor subtype messenger ribonucleic acid expression in clinically nonfunctioning pituitary adenomas.

Little is known about differences in the expression, localization, and function of the two dopamine D2 receptor subtypes, D2short and D2long (D2s and D2l), in either normal or adenomatous pituitary. We investigated the messenger RNA (mRNA) expression of the D2 receptor (D2R) subtypes in clinically nonfunctioning pituitary adenomas by in situ hybridization using subtype-specific oligonucleotides. The five normal pituitaries studied expressed similar ratios of D2R subtypes mRNA with a predominant expression of the D2l isoform. In 2 of 18 clinically inactive adenomas no D2R mRNA was found, whereas in 16 a heterogeneous expression of D2R isoforms was observed. Six adenomas expressed only the D2l and 2 adenomas only the D2s subtype mRNA; the remaining 8 expressed extremely varying proportions of the two subtypes. The D2R was found only in a subset of the nonfunctioning adenoma cells. In gonadotropin-immunopositive adenomas, the D2R was mainly localized in LH- and FSH-immunopositive cells. Probably because of the heterogeneous D2R subtype expression, suppression of cell proliferation was observed in only 3 of 9 adenoma cell cultures in which the growth inhibitory effect of bromocriptine was studied. Although there is some evidence that the presence of the D2s receptor subtype favors the growth inhibitory response to bromocriptine, further studies with a larger number of inactive adenomas are needed to confirm this speculation.

Adenoma↗
PubMed1998

Interleukin-1 beta enhances interleukin-1 receptor antagonist content in human somatotroph adenoma cell cultures.

In addition to the well-known modulation of immune and inflammatory responses, the interleukin-1 (IL-1) system has been shown to be involved in the regulation of anterior pituitary hormone secretion and growth. We previously demonstrated that IL-1 receptor antagonist (IL-1ra) is expressed in human pituitary adenomas cultured in vitro. In the present study, we investigated the regulation of IL-1ra protein by IL-1 beta (1-100 U/mL) in human somatotroph adenomas (n = 9) cultured for 12-48 h. IL-1 beta significantly enhanced the concentration of IL-1ra dose dependently in the somatotroph adenoma cell lysates, whereas IL-1ra concentrations remained unchanged in the culture supernatants. Furthermore, basal IL-1ra concentrations were significantly higher in the cell lysates compared with the corresponding culture supernatants. The regulation of IL-1ra in somatotroph adenoma cells is different from human cultured monocytes, in which IL-1 beta significantly stimulated IL-1ra secretion into the culture supernatants, and no change of intracellular IL-1ra content was observed. Incubation of the somatotroph adenoma cells with 100 U/mL IL-1 beta did not result in a change of GH concentrations in the culture supernatants. Enhancement of intracellular IL-1ra protein by IL-1 beta may represent a mechanism intrinsic to somatotroph adenoma cells to counterregulate the response to IL-1 beta on hormone secretion or cellular growth.

Adenoma↗
PubMed1998

[HNPCC-associated stomach carcinomas display aggressive growth in orthotopic transplantation to the SCID mouse].

The accumulation of malignant tumors in a single family, as well as the early onset of the disease, are highly suggestive of a hereditary condition. The evidence of microsatellite instabilities suggest a disease that might be associated with the HNPCC-syndromee. In contrary to the favourable prognosis of colorectal cancer associated with the HNPCC-syndromee we found in our animal model a far more aggressive progression of the disease in patients with HNPCC-associated gastric carcinomas than in patients with sporadic gastric carcinomas. This observation is consistent with the clinical course. Therefore, gastric carcinomas that are associated with the HNPCC-syndromee seem to represent a separate group of HNPCC-associated carcinomas and may even represent another hereditary disease.

Animals↗
PubMed1998

[Case report of a large lipomatous soft tissue tumor].

A case of diffuse infiltrating lipomatosis is reported. This entity represents a particular type of lipoma. It can be distinguished from other fatty tumors by its localisation, extent, therapeutic procedure, and prognosis. Magnetic resonance imaging (MRI) enables the differentiation from lipomatosis pelvis and malignant tumors as well. Histopathological examination, however, is necessary to exclude liposarcoma. Further growth or recurrence of diffuse infiltrating lipomatosis can be detected by MRI follow-up examinations.

Buttocks↗