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Biomedical subjects

R Schmidt

Publications and source records attributed to R Schmidt.

At least 199 records · Page 11Linked to original sources
PubMed1999

[Antiphospholipid antibody syndrome].

BACKGROUND: Antiphospholipid antibodies comprise a family of auto-antibodies mainly characterized by the presence of the lupus anticoagulant (LA) and anticardiolipin antibodies (ACA). CLINICAL APPEARANCE: The antiphospholipid antibody syndrome is defined by the appearance of frequent thromboses, repeated fetal losses and thrombocytopenia. Other clinical manifestations associated with APA include migraine, chorea, hemolytic anemia, heart valve disease, Budd-Chiari syndrome, perpetual pancreatitic episodes, intestinal infarctions, malignant hypertension, livedo reticularis, pre-eclampsia, fetal growth retardation or catastrophic antiphospholipid syndrome. LA and ACA occur in a variety of clinical conditions (secondary antiphospholipid antibody syndrome, SAPS), including other autoimmune disorders, infectious diseases, neoplastic disorders, in association with the use of certain drugs or in otherwise healthy individuals (primary antiphospholipid antibody syndrome, PAPS). TREATMENT: Patients with thrombosis associated with APA should receive long-term anticoagulation therapy, whereas treatment of asymptomatic patients seems to be not indicated, because only approximately 10% of patients with APA may develop thrombotic complications. In patients with PAPS there is no evidence that the prophylactic administration of immunosuppressive drugs will prevent thromboembolic events.

Antibodies, Antiphospholipid↗
PubMed1999

Physics of rotating gamma systems for stereotactic radiosurgery.

PURPOSE: The purpose of this study was to evaluate the characteristics of a new rotating gamma system for stereotactic radiosurgery by comparison with a well accepted system. METHODS AND MATERIALS: A novel gamma unit for stereotactic radiosurgery has been developed and distributed to 15 hospitals in China. The unit contains 30 cobalt-60 gamma radiation sources with initial activity of 200 Ci (7.4 x 10(12) Bq) each. The sources are positioned along 30 arcs, and rotate continuously as a group in an axis orthogonal to the patient's body. Measurements have been made on a representative unit installed in the Auhai Radiosurgery Center at the Beijing Navy General Hospital in the People's Republic of China. Ionization chambers calibrated by an American accredited dosimetry calibration laboratory were used for these measurements, as well as radiochromic film and thermoluminescent dosimeters. The unit tested utilizes collimators of nominal diameters of 4, 8, 14, and 18 mm. Radiochromic film samples from a Leksell Model U Gamma Knife were evaluated by the same laboratory and are presented for comparison. The treatment planning system was not evaluated. RESULTS: Radiation-absorbed dose rates and profiles measured for this unit are comparable to those previously measured with the same techniques for the Leksell Model U Gamma Knife units in San Diego and Atlanta. CONCLUSION: This unit is capable of producing well collimated beams of high energy photons, suitable for stereotactic radiosurgery. It has similar physical characteristics to those previously reported for the Leksell Model U Gamma Knife unit.

Cobalt Radioisotopes↗
PubMed1999

Headspace gas chromatography-mass spectrometry analysis of isoflurane enantiomers in blood samples after anesthesia with the racemic mixture.

Several in vivo and in vitro studies on the stereoselective potency of isoflurane enantiomers suggest beneficial effects of the (+)-(S)-enantiomer. In order to detect possible differences in the pharmacokinetics of isoflurane enantiomers, a clinical study of 41 patients undergoing general anesthesia maintained with racemic isoflurane was performed. The isoflurane enantiomers were analyzed in blood samples drawn before induction, at cessation (day 0), and up to eight days after isoflurane anesthesia (day 1-8). A multipurpose sampler (Gerstel MPS) was used for the headspace gas chromatography-mass spectrometry (GC/MS) analysis, and it was combined with a cold injection system (Gerstel CIS 3) for coldtrapping, enrichment, and focusing of the analyte. The enantiomer separation was achieved by using a capillary column coated with octakis(3-O-butanoyl-2,6-di-O-pentyl)-gamma-cyclodextrin (Lipodex E) dissolved in the polysiloxane PS 255. Detection was done in the selected ion monitoring mode with ions m/z 117 and m/z 149. An enrichment of (+)-(S)-isoflurane in all blood samples drawn after anesthesia was found. The highest enantiomer bias, up to 52-54% (+)-(S)-isoflurane as compared to 50% for the racemate, was observed on day 2 for most of the patients. Furthermore, quantification of isoflurane in blood samples of five patients was done by enantiomer labeling, employing enantiomerically pure (+)-(S)-isoflurane as internal standard. The isoflurane concentration decreased rapidly from 383 nmol/ml to 0.6 nmol/ml (mean values) eight days after anesthesia. The present study shows differences in the pharmacokinetics of isoflurane enantiomers in man. However, it is not possible to distinguish between enantioselective distribution and enantioselective metabolism, if any.

Anesthesia, Inhalation↗
PubMed1999

[Predictive value of different injured components in ankle fractures].

Injuries of the medial ankle side or the posterior tibial margin do not necessarily predict a negative outcome in ankle fractures, as shown in this comprehensive retrospective study on 342 consecutive patients. A negative predictive value results from the combination of different injured ankle components. Clinical and radiological results correlate well with each other and with the severity of the fracture. They deteriorate according to the number of injured ankle components. Thickening of the soft tissues most often results from complex injuries. It leads to a decrease in range of motion and therefore determines the clinical outcome. Eighty-nine percent of the patients with a personal follow-up and 94 % of those with a written investigation had good to very good results, which represent the upper range of other presentations. This can be achieved by a subtle surgical technique with exact anatomic reduction including primary treatment of at least the severe injuries within the first few hours after trauma. Complications occurred in 9 % of cases, which coincides with the findings of other authors. Especially elderly and obese patients are at higher risk.

Adolescent↗
PubMed1999

[Dynamic gait analysis. Means for quality assurance after surgically treated ankle joint fractures].

Forty-nine patients (mean age, 54 years) admitted for displaced ankle fractures were observed retrospectively to determine by clinical examination and measurement of plantar pressure distribution whether successful surgical treatment of ankle fractures had led to gait symmetry. The mean followup was 36 months (range, 19-54 months). The deviation in gait was quantified using peak pressure. Using a clinical score, most of the patients had satisfactory results. The plantar pressure distribution showed significant load asymmetries of patients with satisfactory results and those with non-satisfactory results. Dynamic gait analysis allows quantification of gait asymmetry and clinically non-visible gait disorder.

Aged↗
PubMed1999

[Indications of cerebral micro-hemorrhage in MRI. Comparative histological findings and possible clinical significance].

Increased use of gradient echo T2*-weighted gradient echo sequences in magnetic resonance imaging (MRI) of patients suffering from primary ICH called attention to foci of signal loss which were suggested to represent remnants of cerebral microbleeds. In a post mortem correlative MR and histopathological study we provide support for this notion. We found areas of signal loss on gradient echo T2*-weighted sequences in 7 out of 11 brains of patients who had died of intracerebral hematoma. Histopathologically, these areas represented hemosiderin deposits indicating previous extravasation of blood. To provide data about the prevalence of these MRI findings in a healthy elderly population a subgroup of participants of the Austrian Stroke Prevention Study was analyzed. We detected foci of signal loss on gradient echo T2*-weighted sequences in 18 out of 280 volunteers (6.4%). MR-based evidence of previous microbleeds may indicate a potentially higher risk of suffering from intracerebral bleeding which could have therapeutic implications for the treatment of acute stroke and for secondary prevention. This hypothesis will have to be tested in future prospective trials.

Aged↗
PubMed1999

Nackt (nkt), a new hair loss mutation of the mouse with associated CD4 deficiency.

A spontaneous recessive mutation named nackt (symbol: nkt) affecting hair growth and T-cell development was discovered in a moderately inbred stock of mice. Skin lesions were characterized by sparse rough coat, bare patches around the eyes and neck, and a scratching behavior throughout life. Fluorescence-activated cell sorter analysis indicated a deficiency in the CD4(+) 8(-) T-cell subset in the thymus and a marked decrease in CD4(+) T cells in peripheral lymphoid organs. Linkage analysis using a set of molecular markers and an F2 intersubspecific cross indicated that the mutation maps to the central region of mouse chromosome 13, in a region homologous to human chromosome 5q22-q35.

Alopecia↗
PubMed1999

A marker-based measurement procedure for unconstrained wrist and elbow motions.

A protocol is proposed to obtain the joint angles of wrist and elbow from tracked triads of surface markers on each limb segment. Cuffs placed on the limb support the rigidity of the triads. Additional markers are used to mark the approximate positions of joints. Corrections of surface marker data for skin motion are derived from a priori knowledge about plausible joint motions. In addition, ill-conditioned states are trapped when the elbow is nearly fully extended. The protocol is applied to sample motions which demonstrate the use and the effect of the corrections. The results show that the model assumptions are reasonable and that accurate joint rotations can be obtained. The correction steps prove to be an essential part of upper-extremity movement analysis.

Adult↗
PubMed1999

A new temporary catheter (ContiCath) for the treatment of temporary, reversible, postoperative urinary retention.

OBJECTIVES: To describe the initial experience of a newly designed temporary urethral catheter, ContiCath, as an aid in the management of postoperative or temporary outflow obstruction. In patients with normal detrusor and sphincter function, this catheter allows volitional voiding while maintaining an open prostatic urethra. METHODS: In a pilot study, 64 nonconsecutive patients with postoperative or temporary urinary retention, at eight clinical trial sites, were enrolled for the placement of this temporary catheter. Three patients did not have the catheter placed because of placement failure because of either a large median lobe or a urethral stricture. The remaining 61 patients were divided into three groups: those with non-neuropathic causes of retention and retention for 1 week or less (37 patients), those with non-neuropathic causes of retention and retention for longer than 1 week (19 patients), and those with neuropathic causes of retention and retention for longer than 1 week (5 patients). The ContiCath is placed in the office setting, in the same fashion as a Foley catheter. A blue prolene tether extends from the bulbar urethra to the meatus to assist in the removal of the device. Patients were then reassessed at 3 hours, and at 7, 14, 21, and 28 days, at which point the device was removed. RESULTS: In patients with a neuropathic cause for their retention (5 patients) and those with non-neuropathic causes of retention and retention for longer than 1 week (19 patients), only 3 patients were able to void after the catheter was placed. Of the 37 patients with a non-neuropathic cause and retention 1 week or less, controlled voiding was seen in 33 patients (89%). Controlled voiding was defined as the patient's volitional ability to initiate and stop his urinary stream. There were no complications with catheter placement; however, 8 patients (24.2%) had minor adverse experiences of frequency/urgency (n = 3), incontinence (n = 3), migration of the catheter (n = 1), and pain (n = 1). CONCLUSIONS: ContiCath offers an alternative to an indwelling Foley catheter in men with temporary bladder outlet obstruction and urinary retention.

Aged↗
PubMed1999

Characterization of [125I]AR-M100613, a high-affinity radioligand for delta opioid receptors.

AR-M100613 ([I]-Dmt-c[-D-Orn-2-Nal-D-Pro-D-Ala-]) is the iodinated analog of a cyclic casomorphin previously shown to be a potent antagonist at the delta opioid receptor. Specific [125I]AR-M100613 binding to rat whole brain membranes was saturable, reversible, and best fit to a one-site model (Kd = 0.080 +/- 0.008 nM, Bmax = 45.2 +/- 4.4 fmol/mg protein). [125I]AR-M100613 binding was displaced with high affinity by the delta opioid receptor ligands SNC-80, Deltorphin II and DPDPE but not the mu or kappa-selective receptor ligands DAMGO and U69593. Residual non-selective binding of [125I]AR-M 100613 to mu opioid receptors is blocked by the addition of CTOP to the assay buffer. [35S]GTPgammaS binding assays indicate that AR-M100613 is a potent, selective, and reversible antagonist for delta opioid receptors in rat brain membranes. The high-affinity, high specific activity, low nonspecific binding and antagonist profile of [125I]AR-M100613 favor its use as a radiochemical probe for delta opioid receptors.

Animals↗
PubMed1999

The arabinose kinase, ARA1, gene of Arabidopsis is a novel member of the galactose kinase gene family.

The arabinose-sensitive ara1-1 mutant of Arabidopsis is deficient in arabinose kinase activity. A candidate for the ARA1 gene. ISA1, has been previously identified through the Arabidopsis genome sequencing initiative. Here we demonstrate that (1) the ARA1 gene coincides with ISA1 in a positional cloning strategy; (2) there are mutations in the ISA1 gene in both the ara1-1 mutant and an intragenic suppressor mutant; and (3) the ara1-1 and suppressor mutant phenotypes can be complemented by the expression of the ISA1 cDNA in transgenic plants. Together these observations confirm that ISA1 is the ARA1 gene. ARA1 is a member of the galactose kinase family of genes and represents a new substrate specificity among this and other families of sugar kinases. A second gene with similarities to members of the galactose kinase gene family has been identified in the EST database. A 1.8 kb cDNA contained an open reading-frame predicted to encode a 496 amino acid polypeptide. The GAL1 cDNA was expressed in a galK mutant of Escherichia coli and in vitro assays of extracts of the strain expressing GAL1 confirmed that the cDNA encodes a galactose kinase activity. Both GAL1 and ARA1 cross-hybridise at low stringency to other sequences suggesting the presence of additional members of the galactose kinase gene family.

Amino Acid Sequence↗
PubMed1999

Surfactant abnormalities in idiopathic pulmonary fibrosis, hypersensitivity pneumonitis and sarcoidosis.

Bronchoalveolar lavage fluids (BALF) from patients with idiopathic pulmonary fibrosis (IPF; n=36), hypersensitivity pneumonitis (HP; n=32) and sarcoidosis (n=44) were investigated for their surfactant properties and compared to healthy control subjects (n=29). The phospholipid (PL) and protein concentration, the PL:protein ratio, PL subclasses, and the surfactant apoproteins (SP)A and SP-B were quantified in BALF. Large surfactant aggregates (LSA) were measured by means of ultracentrifugation and assayed for surface activity using the pulsating bubble surfactometer. As compared to controls, SP-A concentrations, LSA content and PL:protein ratios were significantly decreased in all groups, whereas PL and SP-B concentrations remained unchanged. Changes in the phospholipid profile, with reduced percentages of phosphatidylcholine (not significant) and phosphatidylglycerol and increased fractions of phosphatidylinositol and sphingomyelin (p<0.05), occurred more in IPF than in HP, and not in sarcoidosis. Surface activity was found to be severely impaired in IPF (minimum surface tension (gamma min) approximately 15-20 mN x m(-1)), but only modestly affected in HP and sarcoidosis (gamma min approximately 5 mN x m(-1)) compared to controls (gamma min approximately 0 mN x m(-1)). Reconstitution of pelleted surfactant material with soluble BALF proteins further increased gamma min values. In conclusion, moderate changes in biochemical and physical surfactant properties are encountered in hypersensitivity pneumonitis and sarcoidosis, but pronounced disturbances occur in idiopathic pulmonary fibrosis.

Adolescent↗
PubMed1999

Obstructive uropathy in the mouse: role of osteopontin in interstitial fibrosis and apoptosis.

BACKGROUND: Osteopontin is a macrophage adhesive protein that is expressed by renal tubules in tubulointerstitial disease. METHODS: To investigate the function of OPN, we induced tubulointerstitial disease in OPN null mutant (OPN-/-) and wild-type (OPN+/+) mice by unilateral ureteral ligation. Tissue was analyzed for macrophages (ED-1), types I and IV collagen deposition, TGF-beta expression, and for tubular and interstitial cell apoptosis. RESULTS: Obstructed kidneys from both OPN-/- and OPN+/+ mice developed hydronephrosis, tubular atrophy, interstitial inflammation and fibrosis. OPN was absent in OPN-/- kidneys but was increased in obstructed OPN+/+ kidneys. Macrophage influx, measured by computer-assisted quantitative immunostaining, was less in OPN-/- mice compared to OPN+/+ mice at day 4 (threefold, P < 0.02), day 7 (fivefold, P < 0.02), but not at day 14. Interstitial deposition of types I and IV collagen were also two- to fourfold less in obstructed OPN-/- kidneys (P < 0.02). There was also a reduction of TGF-beta mRNA expression in the interstitium at day 7 (by in situ hybridization) and a near significant 34% reduction in cortical TGF-beta activity (P = 0.06) compared to obstructed OPN+/+ kidneys at day 14. Obstructed kidneys from OPN-/- mice also had more interstitial and tubular apoptotic cells (TUNEL assay) compared to obstructed OPN+/+ mice at all time points. The ability of OPN to act as a cell survival factor was also documented by showing that the apoptosis of serum-starved NRK52E renal epithelial cells was markedly enhanced in the presence of neutralizing anti-OPN antibody. CONCLUSION: OPN mediates early interstitial macrophage influx and interstitial fibrosis in unilateral ureteral obstruction. OPN may also function as a survival factor for renal tubulointerstitial cells.

Animals↗
PubMed1999

Molecular adsorbent recycling system (MARS): clinical results of a new membrane-based blood purification system for bioartificial liver support.

The use of xenogenic or genetically engineered cell types in bioartificial liver support systems requires separation methods between the patients' blood and the liver support bioreactors that guarantee the sufficient transfer of pathophysiologically relevant substances but prevent complications. The present paper describes a new membrane separation system that is nearly impermeable to proteins but enables the exchange of water soluble and protein bound toxins by a special membrane and a recycled protein containing dialysate. Because the full range of toxins in hepatic failure has still not been identified, the value of this membrane separation method was evaluated clinically. Thirteen patients suffering from life threatening hepatic failure who had not responded to state of the art therapy were treated with this device, the molecular adsorbent recycling system (MARS). The overall survival rate was 69%. All patients showed positive response to the therapy, indicating that the presented membrane separator combines therapeutic effectivity with the highest safety criteria for the patient by cutting the exchange of substances below the level of proteins.

Adsorption↗
PubMed1999

Monte Carlo simulations of the imaging performance of metal plate/phosphor screens used in radiotherapy.

The imaging performance of metal plate/phosphor screens which are used for the creation of portal images in radiotherapy is investigated by using Monte Carlo simulations. To this end the modulation transfer function, the noise power spectrum and the detective quantum efficiency [DQE(f)] are calculated for different metals and phosphors and different thicknesses of metal and phosphor for a range of spatial resolutions. The interaction of x-rays with the metal plate/phosphor screen is modeled with the EGS4 electron gamma shower code. Optical transport in the phosphor is modeled by simulating scattering and reabsorption events of individual optical photons. It is shown that metals with a high atomic number perform better than lighter metals in maximizing the DQE(f). It is furthermore shown that the DQE(f) for the metal plate/phosphor screen alone is nearly x-ray quantum absorption limited up to spatial frequencies of 0.4 cycles/mm. In addition, it is argued that the secondary quantum sink of optical photons imposed by the optical chain (mirror, lenses and video camera) leads to a significant degradation of the signal-to-noise ratio at spatial frequencies which are most important for successful registration of portal images. Therefore, the conclusion is that a replacement of the optical chain by a flat array of photodiodes placed directly under the phosphor will lead to a substantial improvement in image quality of portal images.

Algorithms↗
PubMed1999

Purification and characterization of two extremely thermostable enzymes, phosphate acetyltransferase and acetate kinase, from the hyperthermophilic eubacterium Thermotoga maritima.

Phosphate acetyltransferase (PTA) and acetate kinase (AK) of the hyperthermophilic eubacterium Thermotoga maritima have been purified 1,500- and 250-fold, respectively, to apparent homogeneity. PTA had an apparent molecular mass of 170 kDa and was composed of one subunit with a molecular mass of 34 kDa, suggesting a homotetramer (alpha4) structure. The N-terminal amino acid sequence showed significant identity to that of phosphate butyryltransferases from Clostridium acetobutylicum rather than to those of known phosphate acetyltransferases. The kinetic constants of the reversible enzyme reaction (acetyl-CoA + Pi -->/<-- acetyl phosphate + CoA) were determined at the pH optimum of pH 6.5. The apparent Km values for acetyl-CoA, Pi, acetyl phosphate, and coenzyme A (CoA) were 23, 110, 24, and 30 microM, respectively; the apparent Vmax values (at 55 degrees C) were 260 U/mg (acetyl phosphate formation) and 570 U/mg (acetyl-CoA formation). In addition to acetyl-CoA (100%), the enzyme accepted propionyl-CoA (60%) and butyryl-CoA (30%). The enzyme had a temperature optimum at 90 degrees C and was not inactivated by heat upon incubation at 80 degrees C for more than 2 h. AK had an apparent molecular mass of 90 kDa and consisted of one 44-kDa subunit, indicating a homodimer (alpha2) structure. The N-terminal amino acid sequence showed significant similarity to those of all known acetate kinases from eubacteria as well that of the archaeon Methanosarcina thermophila. The kinetic constants of the reversible enzyme reaction (acetyl phosphate + ADP -->/<-- acetate + ATP) were determined at the pH optimum of pH 7.0. The apparent Km values for acetyl phosphate, ADP, acetate, and ATP were 0.44, 3, 40, and 0.7 mM, respectively; the apparent Vmax values (at 50 degrees C) were 2,600 U/mg (acetate formation) and 1,800 U/mg (acetyl phosphate formation). AK phosphorylated propionate (54%) in addition to acetate (100%) and used GTP (100%), ITP (163%), UTP (56%), and CTP (21%) as phosphoryl donors in addition to ATP (100%). Divalent cations were required for activity, with Mn2+ and Mg2+ being most effective. The enzyme had a temperature optimum at 90 degrees C and was stabilized against heat inactivation by salts. In the presence of (NH4)2SO4 (1 M), which was most effective, the enzyme did not lose activity upon incubation at 100 degrees C for 3 h. The temperature optimum at 90 degrees C and the high thermostability of both PTA and AK are in accordance with their physiological function under hyperthermophilic conditions.

Acetate Kinase↗