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R Schmidt

Publications and source records attributed to R Schmidt.

At least 181 records · Page 10Linked to original sources
PubMed2000

Measurement of the dose components of fast and thermal neutrons and photons from a 0.1 mg 252Cf source in water for brachytherapy treatment planning.

The use of 252Cf in brachytherapy is expected to be more effective with the therapy of bulky tumors than the conventional therapy with photons. For treatment planning a code developed for calculation of gamma dose was used to generate the dose distributions of fast and 10B enhanced thermal neutrons and photons. Dose distributions of these components measured with ionization chambers and a GM counter were fitted to analytical functions as required by the modified treatment planning program. A comparison of these experimental results and the treatment planning output indicate good agreement. Therefore, the program may be used to optimize the brachytherapy procedure considering all three dose components. A realistic case of a patient being treated with conventional brachytherapy has been used to calculate the dose distribution that would be obtained by use of the 252Cf source.

Brachytherapy↗
PubMed2000

Apolipoprotein E genotype related differences in brain lesions of multiple sclerosis.

OBJECTIVES: Clinical reports have speculated on a more severe course of multiple sclerosis in patients with the apolipoprotein E (apoE) epsilon4 allele. As this could be reflected by differences in the severity of tissue damage MRI was used to obtain further support for a disease modifying effect of the apoE genotype. METHODS: Brain MR scans of 83 patients (mean age 35.5 (SD 9.5 years) who participated in a cross sectional study on the distribution of genotype patterns in multiple sclerosis. The total lesion load on proton density weighted (T2-LL) and T1 weighted scans (T1-LL) obtained with conventional spin echo sequences at 1.5 T was measured. A "black hole" ratio ((T1-LL/T2-LL)x100) was also calculated. This indicates the proportion of multiple sclerosis lesions with more severe tissue damage and may reflect disease aggressiveness or quality of repair. RESULTS: Patients with the apoE-epsilon3/epsilon4 genotype (n=19) showed a non-significantly greater T2-LL (16.0 (SD 14.0) cm(3)) than patients with the epsilon2/epsilon3 (n=11; 13.3 (9.5) cm(3)) or the epsilon3/epsilon3 genotype (n=49; 9.4 (SD 9.2) cm(3)). Both the T1-LL (2.6 (SD 3.3) v 1.6 (SD 2.4) and 1.2 (SD 3.0) cm(3); p=0.04) and the black hole ratio (14.3 SD 11.9) v 7.4 (SD 9.3) and 8.4 (SD 13.3)%; p=0.02), however, were significantly higher in epsilon3/epsilon4 patients. Similar differences were seen when comparing patients with at least one epsilon4 allele with the remainder of the group. CONCLUSIONS: These data support speculations on a modulation of multiple sclerosis severity by the apoE genotype which can be attributed to more extensive tissue destruction or less efficient repair in carriers of the epsilon4 allele.

Adolescent↗
PubMed2000

MRI cerebral white matter lesions and paraoxonase PON1 polymorphisms : three-year follow-up of the austrian stroke prevention study.

White matter lesions (WMLs) on magnetic resonance imaging (MRI) scans of older persons are thought to be caused by cerebral small-vessel disease. As they progress, these brain abnormalities frequently result in cognitive decline and gait disturbances, and their predictors are incompletely understood. Genetic risk factors have been implicated but remain undetermined so far. We examined whether 2 common polymorphisms of the paraoxonase (PON1) gene leading to a methionine (M allele)-leucine (L allele) interchange at position 54 and an arginine (B allele)-glutamine (A allele) interchange at position 191 are associated with the presence and progression of WMLs. We studied 264 community-dwelling subjects without neuropsychiatric disease (ages 44 to 75 years). All underwent vascular risk factor assessment, brain MRI, and PON1 genotyping. MRI scanning was repeated after 3 years. The extent and number of WMLs were recorded by 3 independent readers. Progression of WMLs was assessed by direct scan comparison. The final rating relied on the majority judgment of the 3 readers. The LL, LM, and MM genotypes were noted in 111 (42.0%), 118 (44.7%), and 35 (13.3%) subjects, respectively; the AA, AB, and BB genotypes occurred in 146 (55.3%), 98 (37.1%), and 20 (7.8%) individuals, respectively. Carriers of the LL genotype showed a nonsignificant trend toward more extensive WMLs and more frequently demonstrated lesion progression over the 3-year observation period (P=0.03). The polymorphism at position 191 had no effect. Logistic regression analysis yielded age (odds ratio, 1.08/y), diastolic blood pressure (odds ratio, 1.05/mm Hg), and LL paraoxonase genotype (odds ratio, 2. 65) to be significant predictors of WML progression. These data suggest that the LL PON1 genotype at position 54 influences the extent and progression of WMLs in elderly subjects.

Adult↗
PubMed2000

Frequency and location of microbleeds in patients with primary intracerebral hemorrhage.

BACKGROUND AND PURPOSE: MRI is known to detect clinically silent microbleeds (MBs) in patients with primary intracerebral hemorrhage (pICH), but the frequency and diagnostic and clinical significance of this finding are still debated. Therefore, we investigated a consecutive series of pICH patients and analyzed the patterns of MB distribution in the context of clinical variables and location of the symptomatic hematoma. METHODS: The study population consisted of 109 patients with pICH. There were 59 women and 50 men aged 22 to 91 years (mean 64.6 years). MRI was obtained on a 1.5-T system with use of a gradient-echo T2*-weighted sequence. A cohort of 280 community-dwelling asymptomatic elderly individuals who underwent the same imaging protocol served for comparison. RESULTS: MBs were seen in 59 (54%) patients and ranged in number from 1 to 90 lesions (mean 14, median 6). In the majority of patients, MBs were located simultaneously in various parts of the brain, with a preference for cortical-subcortical regions (39%) and the basal ganglia/thalami (38%). There was some tendency toward a regional association between MB location and the site of the symptomatic hematoma, but we could not discern specific patterns of MB distribution. Logistic regression analysis identified MBs, periventricular hyperintensity grades, and lacunes but not risk factors as independent variables contributing to a correct classification of pICH and control individuals. CONCLUSIONS: MBs can be detected in more than half of the patients with pICH and appear to be quite general markers of various types of bleeding-prone microangiopathy.

Adult↗
PubMed2000

Osteodensitometry in uncemented total hip arthroplasty using computertomography.

The aim of this investigation was to evaluate a new method developed for the measurement of bone mineral density and bone remodelling phenomena after total hip arthroplasty using computer tomography. Computertomography is a radiological technique to examine bone structures in high resolution. Using an extended scale it is possible to investigate bone scans and implants with fewer metal artifacts. For osteodensitometry measurement a special software (IMPact HIP) for the analysis of the data was used. The measured parameters were the overall bone mineral density (mg Calcium-Hydroxyapatite/ml) and the cortical bone structure. A standard scan mode enable to compare the computertomography scans at follow-up. Nineteen total hip arthroplasty patients (20 hips) with a mean age of 58 years (31-70) were operated on using an uncemented titanium alloy stem with a tapered design. The periprosthetic bone was assessed using computertomography-assisted osteodensitometry two weeks and one year after surgery. We observed a decrease of the overall bone mineral density (15%) and of the cortical bone structure (20%) one year after insertion of the stem in the proximal part of the femur. The area corresponds to the Gruen zones 1 and 7. On the other hand, a decrease of mineral density of 5% for the overall bone and of 3% for the cortical bone was found at the level of the tip of the stem, which corresponds to the Gruen zones 3, 4 and 5. Computertomography-assisted osteodensitometry allows to investigate the bone remodelling after total hip arthroplasty by separating the analysis of the overall bone mineral density and of the cortical structure. The present method is a reliable tool for quality-control in total hip arthroplasty.

Absorptiometry, Photon↗
PubMed2000

[Postoperative wound healing in wound-water contact].

UNLABELLED: The avoiding of water-contact to the freshly closed operation-wound is an unwritten law in surgery. In general, taking a bath or shower is not allowed before wound stitch removal under the idea that early water-contact may lead to a higher wound-infection rate. In a prospective trial 170 patients, operated in our short-stay surgery-unit, were allowed to take a shower 24 hours after surgery. Full water contact of the fresh uncovered wound was accepted. The wound-infection rate in this group was compared with the infection-rate of an historical group from our department (n = 956). RESULTS: In the water-contact group no case of wound-infection was observed while we were observing a wound-infection-rate of 0.6% in the other group. The difference between the two groups wasn't statistically significant (p = 0.125). CONCLUSION: Water-contact of the fresh operation wound 24 hours after surgery did not increase the post-operative wound infection risk in this study.

Adolescent↗
PubMed2000

Frequency of stroke in Europe: A collaborative study of population-based cohorts. ILSA Working Group and the Neurologic Diseases in the Elderly Research Group. Italian Longitudinal Study on Aging.

The authors estimated stroke frequency in Europe using data from six population-based studies that were analyzed separately and also pooled. Overall, these surveys comprised 19,132 individuals age 55 years and older for the prevalence analyses, and 35,577 person-years for the incidence analyses. The overall prevalence of stroke, age- and sex-adjusted to the 1991 European population, was 4.84% (95% CI 4.47 to 5.21) in individuals age 65 to 84 years and 7.06% (95% CI 6.52 to 7.60) in those 75 years and older. Age- and sex-specific rates did not differ substantially across the studies. Incidence rates of first-ever stroke rose markedly with age, and the pooled results confirmed that incidence keeps increasing even at 90 years of age and older. The overall age- and sex-standardized incidence rates were 8.72 per 1000 person-years (95% CI 7.47 to 10.06) for individuals age 65 to 84 years, and 17.31 per 1000 person-years (95% CI 14.79 to 20.02) for those age 75 years and over.

Age Factors↗
PubMed2000

Prognosis with stroke in Europe: A collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group.

The authors pooled four population-based European studies to determine the risk for institutionalization and death after stroke. Risk for institutionalization was assessed in 13,095 subjects. Survival was calculated for prevalent stroke in 7929 individuals and incident stroke in 8550 individuals. The adjusted risk of long-term care for cases compared to noncases was 2.8 (95% CI 2.6 to 4.5). At 5 years, the excess risk of death in prevalent cases was 1.6 (1.2 to 2.0), and the age- and sex-adjusted survival rate was 0.87 compared to 0.91 in noncases. The 5-year survival rate for incident cases was 0.84.

Age Factors↗
PubMed2000

Case-based reasoning for medical knowledge-based systems.

In many domains Case-based Reasoning (CBR) has become a successful technique for knowledge-based systems. In medical domains, attempts to apply the complete CBR cycle are rather exceptional. Some systems have recently been developed, which on the one hand use only parts of the CBR method, mainly the retrieval, and on the other hand enrich the method by a generalisation step to fill the knowledge gap between the specificity of single cases and general rules. So, in this paper we discuss the appropriateness of CBR for medical knowledge-based systems, point out problems, limitations and possibilities how they can partly be overcome.

Artificial Intelligence↗
PubMed1999

Discovery and structure-activity relationships of imidazole-containing tetrahydrobenzodiazepine inhibitors of farnesyltransferase.

2,3,4,5-Tetrahydro-1-(imidazol-4-ylalkyl)-1,4-benzodiazepines were found to be potent inhibitors of farnesyltransferase (FT). A hydrophobic substituent at the 4-position of the benzodiazepine, linked via a hydrogen bond acceptor, was important to enzyme inhibitory activity. An aryl ring at position 7 or a hydrophobic group linked to the 8-position through an amide, carbamate, or urea linkage was also important for potent inhibition. 2,3,4, 5-Tetrahydro-1-(1H-imidazol-4-ylmethyl)-7-(4-pyridinyl)-4-[2-(t rifluo romethoxy)benzoyl]-1H-1,4-benzodiazepine (36), with an FT IC(50) value of 24 nM, produced 85% phenotypic reversion of Ras transformed NIH 3T3 cells at 1.25 microM and had an EC(50) of 160 nM for inhibition of anchorage-independent growth in soft agar of H-Ras transformed Rat-1 cells. Selected analogues demonstrated ip antitumor activity against an ip Rat-1 tumor in mice.

3T3 Cells↗
PubMed1999

The glycine residue in cyclic lactam analogues of galanin(1-16)-NH2 is important for stabilizing an N-terminal helix.

The neuropeptide galanin is a 29- or 30-residue peptide whose physiological functions are mediated by G-protein-coupled receptors. Galanin's agonist activity has been shown to be associated with the N-terminal sequence, galanin(1-16). Conformational investigations previously carried out on full-length galanin have, furthermore, indicated the presence of a helical conformation in the neuropeptide's N-terminal domain. Several cyclic lactam analogues of galanin(1-16)-NH2 were prepared in an attempt to stabilize an N-terminal helix in the peptide. Here we describe and compare the solution conformational properties of these analogues in the presence of SDS micelles as determined by NMR, CD, and fluorescence spectroscopy. Differences in CD spectral profiles were observed among the compounds that were studied. Both c[D4, K8]Gal(1-16)-NH2 and c[D4,K8]Gal(1-12)-NH2 adopted stable helical conformations in the micelle solution. On the basis of the analyses of their respective alpha H chemical shifts and NOE patterns, this helix was localized to the first 10 residues. The distance between the aromatic rings of Trp2 and Tyr9 in c[D4, K8]Gal(1-16)-NH2 was determined to be 10.8 +/- 3 A from fluorescence resonance energy transfer measurements. This interchromophore spacing was found to be more consistent with a helical structure than an extended one. Removal of the Gly1 residue in compounds c[D4,K8]Gal(1-16)-NH2 and c[D4, K8]Gal(1-12)-NH2 resulted in a loss of helical conformation and a concomitant reduction in binding potency at the GalR1 receptor but not at the GalR2 receptor. The nuclear Overhauser enhancements obtained for the Gly1 deficient analogues did, however, reveal the presence of nascent helical structures within the N-terminal sequence. Decreasing the ring structure size in c[D4, K8]Gal(1-16)-NH2 by replacing Lys8 with an ornithine residue or by changing the position of the single lysine residue from eight to seven was accompanied by a complete loss of helical structure and dramatically reduced receptor affinity. It is concluded from the data obtained for the series of cyclic galanin(1-16)-NH2 analogues that both the ring structure size and the presence of an N-terminal glycine residue are important for stabilizing an N-terminal helix in these compounds. However, although an N-terminal helix constitutes a predominant portion of the conformational ensemble for compounds c[D4,K8]Gal(1-16)-NH2 and c[D4, K8]Gal(1-12)-NH2, these peptides nevertheless are able to adopt other conformations in solution. Consequently, the correlation between the ability of the cyclic galanin analogues to adopt an N-terminal helix and bind to the GalR1 receptor may be considered as a working hypothesis.

Alanine↗
PubMed1999

Functional attributes discriminating mechano-insensitive and mechano-responsive C nociceptors in human skin.

Microneurography was used in healthy human subjects to record action potentials from unmyelinated nerve fibers (C units) in cutaneous fascicles of the peroneal nerve. Activity-dependent slowing (n = 96) and transcutaneous electrical thresholds (n = 67) were determined. Eight units were sympathetic efferents according to their responses to sympathetic reflex provocations. Mechano-heat-responsive C units (CMH) (n = 56) had thresholds to von Frey hair stimulation </=90 mN (6.5 bar). Mechano-insensitive C units (n = 32) were unresponsive to 750 mN (18 bar). Twenty-six mechano-insensitive units responded to heat (CH), and the remaining six units did not respond to physical stimuli but were proven to be afferent by their response to intracutaneous capsaicin (CM(i)H(i)). Mechano-insensitive units had significantly slower conduction velocity (0.81 +/- 0.03 m/sec), and CH units had higher heat thresholds (48.0 +/- 0.6 degrees C) compared with CMH units (1.01 +/- 0.01 m/sec; 40.7 +/- 0.4 degrees C). Transcutaneous electrical thresholds were <9 mA for CMH units and >35 mA for CH and CM(i)H(i) units. Activity-dependent slowing was much more pronounced in mechano-insensitive than in mechano-responsive units, without overlap. Sympathetic efferent C units showed intermediate slowing, significantly different from CMH, and completely separate from CH and CM(i)H(i) units. The activity-dependent slowing of conduction provides evidence for different membrane attributes of different classes of C fibers in humans.

Adult↗
PubMed1999

Inverse association between endogenous glucocorticoid secretion and L-selectin (CD62L) expression in trauma patients.

Exogenously administered glucocorticoids downregulate inflammatory host response, i.e. by inhibition of adhesion molecule expression on leukocyte surfaces. Here, possible associations between the trauma-induced endogenous secretion of cortisol and the expression of neutrophil adhesion molecules (L-selectin/CD62L, CD 11b, CD54) were studied in humans. Standardized elective hip arthroplasty was investigated as an exemplary condition of acute inflammation. In 20 patients, blood for quantification of cortisol and adrenocorticotropic hormone was obtained at minutes 10, 20, 30, 60, hours 1, 2, 4 and 10 and days 1,3 and 7. Expression of L-selectin/CD62L, CD11b and CD54 on neutrophil surfaces was determined preoperatively, and postoperatively at hours 1, 2, 3, 4, and 10 and at days 1 and 3. Secretion of both, adrenocorticotropic hormone and cortisol was significantly increased between 1-10 hours after onset of tissue injury. Compared to baseline values, CD11b expression was increased at hour 1 and normalized after day 1, whereas L-selectin/CD62L expression, mirroring this pattern was decreased until day 1. Patients with high endogenous glucocorticoid secretion exhibited significantly decreased expression selectively of L-selectin/CD62L. However, we also observed that glucocorticoids do not directly induce L-selectin shedding from neutrophil surfaces in vitro, arguing for more indirect glucocorticoid action on adhesion molecule expression. Together, this study showed that increased endogenous cortisol secretion is associated with lower expression of L-selectin on neutrophil surfaces in humans that is consistent with a downmodulating role of this neuroendocrine stress response in inflammatory leukocyte recruitment.

Adrenocorticotropic Hormone↗
PubMed1999

MRI white matter hyperintensities: three-year follow-up of the Austrian Stroke Prevention Study.

OBJECTIVE: To determine the rate, clinical predictors, and cognitive consequences of MRI white matter hyperintensity evolution over 3 years. METHODS: In the setting of the Austrian Stroke Prevention Study, 1.5-T MRI was performed at baseline and at a 3-year follow-up in 273 community-dwelling elderly (mean age, 60+/-6.1 years) without neuropsychiatric disease. At each visit individuals underwent a structured clinical interview and examination, EKG, echocardiography, extensive laboratory workup, and demanding neuropsychological testing. MR images were read by three independent raters, and the change of white matter hyperintensities from baseline was assessed by direct image comparison. The change was graded as absent, minor, or marked. Minor change was defined as a difference of no more than one to four punctate lesions between both scans. A change was considered to be marked if there was a difference of more than four abnormalities or a transition to early-confluent and confluent lesions. RESULTS: Combined ratings indicated lesion progression in 49 individuals (17.9%). Lesion progression was minor in 27 participants (9.9%) and was marked in 22 (8.1%). Regression of white matter hyperintensities did not occur. Diastolic blood pressure (odds ratio, 1.07/mm Hg) and early-confluent or confluent white matter hyperintensities at baseline (odds ratio, 2.62) were the only significant predictors of white matter hyperintensity progression. Lesion progression had no influence on the course of neuropsychological test performance over the observational period. CONCLUSIONS: White matter hyperintensities progress in elderly normal subjects. Our data may be used as a reference for future observational and interventional studies on white matter hyperintensity progression in various CNS diseases. The lack of an association between lesion progression and cognitive functioning needs to be explored further.

Aged↗
PubMed1999

MRI evidence of past cerebral microbleeds in a healthy elderly population.

BACKGROUND: Incidental foci of signal loss suggestive of past microbleeds are a frequent finding on gradient-echo T2-weighted MRI of patients with nontraumatic intracerebral hemorrhage and have been associated with bleeding-prone microangiopathy. If and to what extent such lesions may also occur in the normal population is unclear. OBJECTIVE: To determine focal hypointensities in asymptomatic elderly individuals and their relation to other clinical and morphologic variables. METHODS: T2-weighted MRI of the brain was performed in a consecutive series of 280 participants (mean age 60 years, range 44 to 79) of the Austrian Stroke Prevention Study. This cohort consisted of randomly selected individuals without history or signs of neuropsychiatric disorder. RESULTS: Past microbleeds ranging from one to five foci of signal loss were seen in 18 (6.4%) individuals. They were strongly associated with higher age, hypertension, and lacunes (p < 0.001), and extensive white matter damage was more frequently noted (p = 0.02). Hypertension was present in all individuals with focal hypointensities in the basal ganglia and infratentorially but in only 5 of 10 volunteers with microbleeds limited to cortico-subcortical sites (p = 0.04). CONCLUSIONS: MRI evidence of past microbleeds may be found even in neurologically normal elderly individuals and is related, but not restricted, to other indicators of small vessel disease. The predictive potential of this finding regarding the risk of intracerebral bleeding requires further investigation.

Aged↗