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R Schmidt

Publications and source records attributed to R Schmidt.

At least 163 records · Page 9Linked to original sources
PubMed2000

Novel Dmt-Tic dipeptide analogues as selective delta-opioid receptor antagonists.

A series of Dmt-Tic analogues with substitution on the Tic aromatic ring has been synthesized and evaluated for opioid receptor affinity and activation. Incorporation of large hydrophobic groups at position 7 of Tic did not greatly alter the delta opioid receptor binding affinities of the dipeptides whereas substitution at position 6 substantially diminished their affinity. These modified Dmt-Tic peptides showed binding affinities as low as 2.5 nM with up to 500-fold selectivity for the delta versus mu opioid receptor and proved to be delta receptor antagonists.

Benzamides↗
PubMed2000

Sonography of palpable breast cancer.

PURPOSE: Because of the increasing use of sonography to rule out cancer in women with palpable breast abnormalities, this study was performed to determine the rate of sonographically occult malignancy in this clinical setting. METHODS: Women who were recommended for biopsy based on mammographic and/or clinical findings underwent breast sonography. This study retrospectively analyzed the subset of patients with palpable malignant lesions. Lesions were classified as visible or occult on mammography and sonography. Patients without a tissue diagnosis of tumor were excluded. RESULTS: Of 1,346 masses that underwent biopsy or aspiration, 616 lesions were palpable, and of these, 293 were malignant. Sonography detected all 293 palpable malignant lesions (95% confidence interval for sensitivity, 99-100%). Eighteen lesions were mammographically occult. The median lesion size as determined by sonography was 1.8 cm; for the lesions that were mammographically occult, the median size was 1.6 cm. The most common histopathologic diagnosis for both groups of lesions was infiltrating ductal carcinoma. CONCLUSIONS: All palpable malignant breast lesions were visible by sonography in patients in whom a biopsy was recommended. However, we caution that until the false-negative rate of sonography for equivocal palpable abnormalities is determined prospectively, sonography cannot be accurately applied to rule out malignancy in this setting.

Adolescent↗
PubMed2000

Separation and absolute configuration of the enantiomers of a degradation product of the new inhalation anesthetic sevoflurane.

In a rebreathing anesthesia circuit, the inhaled anesthetic sevoflurane degrades into at least two products, termed "compound A" and "compound B." The enantiomer separation of the chiral compound B (1,1,1,3,3-pentafluoro-2-(fluoromethoxy)-3-methoxypropane ) by capillary gas chromatography (cGC) using heptakis (2,3-di-O-acetyl-6-O-tert-butyldimethylsilyl)-beta-cyclodextrin as chiral selector was studied. With this cyclodextrin derivative diluted in the polysiloxane PS 86, an unprecedented high separation factor alpha of 4.1 (at 30 degrees C) was found. Consequently, the enantiomers of compound B were isolated by preparative GC and their specific rotations were measured. In addition, their absolute configurations were determined by X-ray crystallography. To collect the X-ray data, single crystals of both enantiomers were grown in situ on the diffractometer. The levorotatory enantiomer B(-) has the R-configuration while the dextrorotatory enantiomer B(+) has the S-configuration. The elution order of the compound B enantiomers on heptakis (2,3-di-O-acetyl-6-O-tert-butyldimethylsilyl)-beta-cyclodextrin is R before S.

Anesthetics, Inhalation↗
PubMed2000

Improvement of hepatorenal syndrome with extracorporeal albumin dialysis MARS: results of a prospective, randomized, controlled clinical trial.

In hepatorenal syndrome (HRS), renal insufficiency is often progressive, and the prognosis is extremely poor under standard medical therapy. The molecular adsorbent recirculating system (MARS) is a modified dialysis method using an albumin-containing dialysate that is recirculated and perfused online through charcoal and anion-exchanger columns. MARS enables the selective removal of albumin-bound substances. A prospective controlled trial was performed to determine the effect of MARS treatment on 30-day survival in patients with type I HRS at high risk (bilirubin level, > or =15 mg/dL) compared with standard treatment. Thirteen patients with cirrhosis with type I HRS were included from 1997 to 1999. All were Child's class C, with Child-Turcotte-Pugh scores of 12.4 +/- 1. 0, United Network for Organ Sharing status 2A, and total bilirubin values of 25.7 +/- 14.0 mg/dL. Eight patients were treated with the MARS method in addition to hemodiafiltration (HDF) and standard medical therapy, and 5 patients were in the control group (HDF and standard medical treatment alone). None of these patients underwent liver transplantation or received a transjugular intrahepatic portosystemic shunt or vasopressin analogues during the observation period. In the MARS group, 5.2 +/- 3.6 treatments (range, 1 to 10 treatments) were performed for 6 to 8 hours daily per patient. A significant decrease in bilirubin and creatinine levels (P <.01) and increase in serum sodium level and prothrombin activity (P <.01) were observed in the MARS group. Mortality rates were 100% in the control group at day 7 and 62.5% in the MARS group at day 7 and 75% at day 30, respectively (P <.01). We conclude that the removal of albumin-bound substances with the MARS method can contribute to the treatment of type I HRS.

Albumins↗
PubMed2000

Genetic aspects of microangiopathy-related cerebral damage.

Microangiopathy related cerebral damage (MARCD) includes early confluent and confluent white matter hyperintensities (WMH) and lacunar lesions. It is expected to be the result of interactions between multiple genetic and environmental factors. The estimated proportion of genetic factors contributing to the interindividual variation seen in WMH volume is 73%. This estimate points to a significant genetic component in WMH development. In the setting of the Austrian Stroke Prevention Study we search for genes being associated with the presence, severity and progression of MARCD using the candidate gene approach. Defining susceptibility genes may allow to better identify individuals at high risk for MARCD and to target preventive measures.

Apolipoprotein E2↗
PubMed2000

Novel imaging technologies in the assessment of cerebral ageing and vascular dementia.

Introduction of magnetic resonance imaging (MRI) has opened new possibilities for detecting age-related brain tissue changes. The majority of these abnormalities consists of hyperintense foci in the deep and subcortical white matter probably related to microvascular disturbances and of signal hyperintensities around the lateral ventricles. It has also been suggested that these abnormalities may contribute to the development of cognitive impairment. The correlation between age-related signal abnormalities on conventional MRI and neuropsychologic dysfunction is limited, however, and a threshold beyond which such a relation may come into existence has not yet been defined. Poor tissue characterisation by conventional MRI may be one explanation. Therefore, new pulse sequences are expected not only to provide a higher lesion contrast such as the fluid attenuated inversion recovery (FLAIR) technique but also to offer new insights concerning the composition of incidental brain lesions. In this context both magnetisation transfer imaging (MTI) and diffusion weighted imaging (DWI) may serve to gain information about the integrity of cell membranes and organelles and the preservation of axons and fibre tracts. We will review the technical background of these recently developed MR sequences and their first applications to age-associated brain abnormalities.

Aging↗
PubMed2000

[Acute retinpathia praematurorum. Is plasma prorenin level of prognostic value?].

BACKGROUND: In patients with diabetes mellitus an elevated level of plasma prorenin (PP) may be associated with proliferative diabetic retinopathy. Although retinopathy of prematurity (ROP) is also characterized by retinal vasoproliferation, no study on PP in ROP appears to have been carried out. This study investigated PP prospectively in preterm infants with high risk of ROP. PATIENTS AND METHODS: In 304 preterm infants (gestational age 24-36 weeks, mean +/- SD 29.8 +/- 2.6 weeks; birth weight 570-1750 g, 1180 +/- 294 g) PP was examined prospectively between 3 and 14 weeks postnatally. Renin and total renin (after cryoactivation) were determined by radioimmunoassay. Total renin minus renin is the PP level; PP was correlated with the presence of ROP, stage of ROP, gestational age, birth weight, and postnatal age. RESULTS: There was no significant difference between mean PP in 112 preterm infants with ROP (682 +/- 666 ng/l) and that in 192 preterm infants without ROP (622 +/- 454 ng/l). There was no correlation between PP and the stage of ROP, gestational age, or birth weight. Mean PP decreased with increasing postnatal age (postnatal age 3-4 weeks: 906 +/- 587 ng/l; 7-8 weeks: 585 +/- 423 ng/l; 13-14 weeks: 326 +/- 205 ng/l). CONCLUSION: This study found no significant difference in PP between preterm infants with and those without ROP. Thus PP is not a valid predictor or indicator of ROP. However, the study showed a hitherto unknown correlation between PP and postnatal age in preterm infants.

Birth Weight↗
PubMed2000

Vascular risk factors in dementia.

This review describes differing profiles of vascular risk factors in different types of dementia. Although vascular risk factors are related to various types of strokes, their independent effect on the occurrence of poststroke dementia appears to be small. Various risk factors have been identified for microangiopathy-related cerebral abnormalities, such as white matter changes and lacunae, which are the core lesions for the development of a vascular dementia syndrome without stroke symptoms. Most consistently, arterial hypertension and diabetes mellitus have been found to be associated with such brain abnormalities. Diastolic blood pressure seems to be of particular importance as recent investigations demonstrate that this factor is related to the course of multiple lacunar strokes and the progression of white matter disease. Epidemiological studies report that various vascular risk factors including arterial hypertension, diabetes mellitus, and atrial fibrillation may also be associated with Alzheimer's disease. There is also evidence of a direct relationship between Alzheimer's disease and general atherosclerosis. Further investigations are needed to determine whether these associations are due to the weakness of diagnostic criteria, or whether vascular risk factors indeed modulate the clinical expression of primary degenerative dementia. Common susceptibility genes leading to shared risk factors may be one of the reasons for a higher coincidence of Alzheimer's disease and vascular dementia than can be expected by chance. A modulatory effect of vascular risk factors in the development of primary degenerative dementia may extend treatment options.

Aged↗
PubMed2000

Movement biomechanics goes upwards: from the leg to the arm.

The analysis of lower limb movements has been well established in biomechanics research and clinical applications for a long time. For these studies, powerful and very advanced tools have been developed to measure movement parameters and reaction forces. The main focus of interest aims towards gait movements while the understanding of the basic concepts is supported by numerous models. Definitions of physiological ranges and detection of pathological changes in movements open an increasingly valuable clinical field of application. If, however, the primary function of the upper extremities as highly variable and adaptive organ for manipulating tasks is the subject of interest, the situation becomes considerably more complex. The nature of free arm movements is completely different from being restricted, repeatable or cyclic as compared to gait. Therefore, the transfer of the knowledge and experience gained in lower extremity movement analysis to the analysis of upper extremities turns out to be difficult. A proposal for how to proceed in measurements, e.g. where to place the markers and how to calculate movements and angles of segments involved, will be discussed which results in the description of the joint movements of wrist, elbow and shoulder joint. The definition of the motion is a specific step in upper extremity motion analysis which is important in terms of repeatability and significance of the results. An example of assessing movement disorders in children with plexus lesion will illustrate the implications and the potential of upper extremity movement analysis in clinical applications.

Arm↗
PubMed2000

Mechano-insensitive nociceptors encode pain evoked by tonic pressure to human skin.

Single unmyelinated axons in the superficial branch of the peroneal nerve of human subjects were recorded (microneurography) and the response patterns during tonic pressure stimulation (14N at 30 mm(2); 120 s) were assessed using the previously described "marking technique". It was found that tonic pressure stimuli induced augmenting pain responses which were matched by the discharges of initially mechano-insensitive ("silent") C-units, whereas mechano- and heat-responsive "polymodal" C-nociceptors showed a response pattern incompatible with the stimulus-induced perceptions, namely strong initial excitation, followed by adaptation. Eighteen mechano- and heat-responsive "polymodal" C-fibers and 11 mechano-insensitive units were studied. The former had von Frey thresholds <160 mN, the latter were not excited by a von Frey filament of 750 mN (six of them responded to radiant heat stimulation). However, in the course of pressure stimulation, nine of the 11 mechano-insensitive units were activated after more than 20s. A second, identical pressure stimulus induced a stronger response in mechano-insensitive and a weaker response in mechano-responsive units. The stronger response, indicating sensitization, matched the more intense pain perception during the second pressure stimulus. It is concluded that mechano-insensitive C-nociceptors encode pressure-induced pain in human hairy skin and that they play an important role in static mechanical hyperalgesia.

Adult↗
PubMed2000

Synteny: recent advances and future prospects.

Their small sizes have meant that the Arabidopsis and rice genomes are the best-studied of all plant genomes. Although even closely related plant species can show large variations in genome size, extensive genome colinearity has been established at the genetic level and recently also at the gene level. This allows the transfer of information and resources assembled for rice and Arabidopsis to be used in the genome analysis of many other plants.

Arabidopsis↗
PubMed2000

Human neutralizing monoclonal antibodies of the IgG1 subtype protect against mucosal simian-human immunodeficiency virus infection.

Although maternal human immunodeficiency virus type 1 (HIV-1) transmission occurs during gestation, intrapartum and postpartum (by breast-feeding), 50-70% of all infected children seem to acquire HIV-1 shortly before or during delivery. Epidemiological evidence indicates that mucosal exposure is an important aspect of intrapartum HIV transmission. A simian immunodeficiency virus (SIV) macaque model has been developed that mimics the mucosal exposure that can occur during intrapartum HIV-1 transmission. To develop immunoprophylaxis against intrapartum HIV-1 transmission, we used SHIV-vpu+ (refs. 5,6), a chimeric simian-human virus that encodes the env gene of HIV-IIIB. Several combinations of human monoclonal antibodies against HIV-1 have been identified that neutralize SHIV-vpu+ completely in vitro through synergistic interaction. Here, we treated four pregnant macaques with a triple combination of the human IgG1 monoclonal antibodies F105, 2G12 and 2F5. All four macaques were protected against intravenous SHIV-vpu+ challenge after delivery. The infants received monoclonal antibodies after birth and were challenged orally with SHIV-vpu+ shortly thereafter. We found no evidence of infection in any infant during 6 months of follow-up. This demonstrates that IgG1 monoclonal antibodies protect against mucosal lentivirus challenge in neonates. We conclude that epitopes recognized by the three monoclonal antibodies are important determinants for achieving substantial protection, thus providing a rational basis for AIDS vaccine development.

Animals↗
PubMed2000

Comparative genome analysis reveals extensive conservation of genome organisation for Arabidopsis thaliana and Capsella rubella.

Genome colinearity has been studied for two closely related diploid species of the Brassicaceae family, Arabidopsis thaliana and Capsella rubella. Markers mapping to chromosome 4 of A. thaliana were found on two linkage groups in Capsella and colinear segments spanning more than 10 cM were revealed. Detailed analysis of a 60 kbp region in A. thaliana and its counterpart in C. rubella showed virtually complete conservation of gene repertoire, order and orientation. The comparison of orthologous genes revealed very similar exon-intron structures and sequence identities of 90% or more were found for exon sequences. This extensive genome colinearity at the genetic and molecular level allows the efficient transfer of data from the well-studied A. thaliana genome to other species in the Brassicaceae family, substantially facilitating genome analysis studies for species of this family.

Amino Acid Sequence↗
PubMed2000

Isolation of Mycoplasma meleagridis from free-ranging birds of prey in Germany.

In this study tracheal swabs and air sac biopsies of 68 raptors of different species that were found injured or debilitated in Germany were investigated for the occurrence of mycoplasmas. Mycoplasma meleagridis, Mycoplasma falconis, Mycoplasma buteonis, Mycoplasma gypis and five mycoplasma isolates not identified so far could be isolated from 32 (47%) birds. Mycoplasma meleagridis could be detected in five birds. These birds did not show clinical signs or histopathological alterations in air sac biopsies related to the infection.

Air Sacs↗
PubMed2000

Liver support by extracorporeal blood purification: a clinical observation.

Liver failure associated with excretory insufficiency and jaundice results in an endogenous accumulation of toxins involved in the impairment of cardiovascular, kidney, and cerebral function. Moreover, these toxins have been shown to damage the liver itself by inducing hepatocellular apoptosis and necrosis, thus creating a vicious cycle of the disease. We report a retrospective cohort study of 26 patients with acute or chronic liver failure with intrahepatic cholestasis (bilirubin level > 20 mg/dL) who underwent a new extracorporeal blood purification treatment. A synthetic hydrophilic/hydrophobic domain-presenting semipermeable membrane (pore size < albumin size, 100-nm thick) was used for extracorporeal blood detoxification using dialysis equipment. The opposite side was rinsed with ligandin-like proteins as molecular adsorbents that were regenerated online using a chromatography-like recycling system (molecular adsorbent recirculating system [MARS]). Bile acid and bilirubin levels, representing the previously described toxins, were reduced by 16% to 53% and 10% to 90% of the initial concentration by a single treatment of 6 to 8 hours, respectively. Toxicity testing of patient plasma onto primary rat hepatocytes by live/dead fluorescence microscopy showed cell-damaging effects of jaundiced plasma that were not observed after treatment. Patients with a worsening of Child-Turcotte-Pugh (CTP) index before the treatments showed a significant improvement of this index during a period of 2 to 14 single treatments with an average of 14 days. After withdrawal of MARS treatment, this improvement was sustained in all long-term survivors. Ten patients represented a clinical status equivalent to the United Network for Organ Sharing (UNOS) status 2b (group A1), and all survived. Sixteen patients represented a clinical status equivalent to UNOS status 2a, and 7 of these patients survived (group A2), whereas 9 patients (group B) died. We conclude that in acute excretory failure caused by a chronic liver disease, this treatment provides a therapy option to remove toxins involved in multiorgan dysfunction secondary to liver failure.

Adult↗