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Biomedical subjects

R Schmidt

Publications and source records attributed to R Schmidt.

At least 37 records · Page 2Linked to original sources

[Managing patients with dementia--current status and formulating dementia policy desiderata and options ].

The demographic and epidemiological scenarios, concerning persons with dementia, are in tension between the legal general conditions of care, on the one hand, and the conceptual alignment, on the other hand; this tension is hardly resolved by the momentary activities in health and care policy. Even on the level of assessment, there are scarcely any instruments to picture the specific needs of patients with dementia. Concepts of supply for persons with dementia are widely still divided by the differentiation between stationary and outpatient. Intelligent mixtures and paradigmatic reorientation towards normalization or split responsibility have not yet enfolded their embossing effects in practice. The care of persons with dementia is in many respects still bound in pre-technical constellations: this applies to the conceptual bias inside an institution or service of old people's care, to legal and economical general conditions and instruments of control and in many ways also to the technical discourse. The relevancy of attendance of people with dementia today and in the future justifies talking about "dementia policy". Options for dementia policy lay in a consequent adaptation of the theory of the New Welfare Mix, which was developed by the political sciences, including discussion about normalization in the area of help for disabled people and in the reformulation of competence between the means of fringe benefits and employees' benefits in joint responsibility.

Aged↗

Removal of NAPLs from the unsaturated zone using steam: prevention of downward migration by injecting mixtures of steam and air.

Steam injection for remediation of porous media contaminated by nonaqueous phase liquids has been shown to be a potentially efficient technology. There is, however, concern that the technique may lead to downward migration of separate phase contaminant. In this work, a modification of the steam injection technology is presented, where a mixture of steam and air was injected. In two-dimensional experiments with unsaturated porous medium contaminated with nonaqueous phase liquids, it was demonstrated how injection of pure steam lead to severe downward migration. Similar experiments, where steam and air were injected simultaneously, resulted in practically no downward migration and still rapid cleanup was achieved. The processes responsible for the prevention of downward migration when injecting steam-air mixtures were analyzed using a nonisothermal multiphase flow and transport model. Hereby, three mechanisms were identified and it was demonstrated how the effectiveness of these mechanisms depended on the air-to-steam mixing ratio.

Air↗

Chronic stress induces opposite changes in the mRNA expression of the cell adhesion molecules NCAM and L1.

The effects of 21-day exposure to restraint stress on mRNA levels of the cell adhesion molecules NCAM and L1 were evaluated in different hippocampal regions (CA1, CA3, and dentate gyrus) and other structures (thalamus, prefrontal and frontal cortices, and striatum) of the rat brain. A general decrease in gene expression of the neural cell adhesion molecule (NCAM) was found throughout the brain, particularly in all hippocampal subregions. On the contrary, transcripts for the adhesion molecule L1 were specifically increased at the level of the hippocampus, especially in the dorsal dentate gyrus and area CA3. mRNA for the NCAM180 isoform was detected unchanged in all brain areas examined after chronic stress. A second experiment explored whether there would be cognitive alterations associated with this stress procedure and molecular regulation. Thus, after exposure to the same restraint regimen, performance in the water maze was evaluated. Although stressed rats displayed the ability to learn the task throughout the training session, they showed a transient deficit in the initial phase of the acquisition. In conclusion, our findings indicate that chronic stress interferes with the mechanisms involved in the synthesis of cell adhesion molecules of the immunoglobulin superfamily. Furthermore, they suggest that these effects might be involved in the mechanisms by which stress induces structural and functional alterations in the central nervous system and, particularly, in the hippocampus.

Animals↗

Protein A immunoadsorption in a pregnant woman with habitual abortion.

The role of antibodies in the occurrence of recurrent spontaneous miscarriage is well known. However there are many controversial issues in the management of habitual abortion. This paper describes the effect of Protein A immunoadsorption on serum levels of these antibodies and its impact on a case of a successfully treated woman in a outpatient department without need for a central venous catheter. Given the favourable clinical results described in our paper we think it may be relevant for some worse cases in clinical practice and will interest your readers.

Abortion, Habitual↗

Accumulation of S(+) enantiomer in human beings after general anaesthesia with isoflurane racemate.

BACKGROUND AND OBJECTIVE: Isoflurane is a chiral, volatile anaesthetic with low metabolic rate (0.17%) that is routinely administered in its racemic form. Knowledge about the distribution of the enantiomers in human beings may give some important information about the understanding of the mechanisms of volatile anaesthetics. METHODS: Blood samples were drawn immediately after tracheal extubation and daily up to 8 days postoperatively from patients undergoing general anaesthesia with isoflurane racemate. The enantiomer enrichment of isoflurane was determined by headspace gas chromatography-mass spectrometry. RESULTS: At all time points, there was a statistically significant accumulation of the S(+) enantiomer in blood, especially at days 2 (52.01%) and 7 (52.1%). Separate analysis of obese patients or in a small group of patients with co-existing lung disease did not show any difference to the total population. In addition, duration of anaesthesia did not influence the enantiomer concentrations. CONCLUSIONS: We suggest that a slower association and dissociation rate is responsible for the S(+) enrichment.

Aged↗

Improvement in central nervous system functions during treatment of liver failure with albumin dialysis MARS--a review of clinical, biochemical, and electrophysiological data.

The Molecular Adsorbent Recirculating System (MARS) is a nonbiological liver support method based on the principles of dialysis, filtration, and adsorption. It allows the safe and efficient removal of both albumin-bound and water-soluble toxic metabolites, including ammonia, aromatic amino acids, tryptophan, and related phenolic and indolic products, as well as benzodiazepines. A well-documented effect of the treatment is the improvement of the hemodynamic situation of decompensated chronic patients. Systemic vascular resistance, mean arterial pressure, cerebral blood flow, and cerebral oxygen consumption increased significantly. The degree of hepatic encephalopathy decreased significantly. Increased intracranial pressure could be normalized in both chronic and fulminant liver failure. In three randomized clinical trials significant improvement of survival could be demonstrated. In a model of murine neuronal networks cultured on multi-microelectrode array plates and incubated with plasma from liver failure patients, a normalization of the spike and burst pattern could be observed, if plasma samples from MARS-treated patients before and after treatment were compared. In conclusion, MARS significantly improves central nervous system functions. It can serve as a model for the further investigation of the role of protein-bound substances in hepatic encephalopathy and cerebral hemodynamics.

Brain↗

Immunoadsorption of sensitized kidney transplant candidates immediately prior to surgery.

Patients with anti-human leucocyte antigen (HLA) antibodies from previous transplantation, blood transfusion are highly sensitized and at risk to hyperacute renal graft loss. As these antibodies are identified to be of pathogenic importance, an effective removal may allow successful transplantation. Six 'high risk patients' [panel-reactive antibodies (PRA) >30% or retransplanted patients with an acutely rejected first graft within 6 months from surgery] were treated by protein A immunoadsorption (IA) immediately prior to transplantation. We treated the calculated plasma volume one to three times prior to surgery: mean 4600 mL (range 2100-10 200 mL). After transplantation we repeated the sessions according to antibody (Ab) recurrence, graft function and signs of rejection. The panel reactive Ab were reduced from mean 65% pre-IA (range 35-85) to lowest 15% (range 0-55). After the course they reappeared to 30% (range 0-90). Five of the six patients had no clinical signs of vascular rejection. At a follow-up of mean 54 months (+/-14) four grafts still function with a mean serum creatinine of 172 micromol/L (+/-57). Protein A IA is a safe and effective adjunct in the treatment of highly sensitized patients awaiting renal transplantation. The treatment immediately prior to operation can prevent hyperacute rejection and increases the graft survival in these patients.

Adult↗

Amino acid dysbalance in liver failure is favourably influenced by recirculating albumin dialysis (MARS).

INTRODUCTION: Dysbalance between branched chain (BCAA) and aromatic amino acids (AAA), which can be quantified by a low Fischer's Index (SigmaBCAA/SigmaAAA), as well as elevated levels of free tryptophan in plasma are common in hepatic failure and may contribute to the development of hepatic encephalopathy. AIM: To evaluate the influence of a new extracorporeal detoxification system for liver failure (Molecular Adsorbents Recirculating System, MARS(R), i.e. dialysis against a recirculating albumin solution cleaned online by charcoal and an anion exchange resin) on plasma tryptophan and Fischer's Index. METHODS: Plasma samples were taken before, during and after MARS treatments (n = 11, mean blood flow 135 ml/min, mean dialysate flow 120 ml/min, high flux polysulfone membrane). Simultaneous to blood sampling, aliquots of the albumin dialysate were taken between the elements of the dialysate circuit. RESULTS: Fischer's Index in systemic blood increased during MARS by 24% (from 1.44 to 1.79, P < 0.001; mean treatment duration, 5.5 h). Systemic tryptophan level was significantly reduced at the same time (-25%, n = 8). Amino acid removal rates from plasma during a single dialyser passage ranged from 10 to 53%. In particular, AAA were preferentially removed (42-44% throughout treatment), while BCAA removal was 28-46% initially and later declined to 24-28%. A maximum concentration gradient between plasma and dialysate was maintained for the AAA throughout treatment through their apparently complete removal by the charcoal adsorber. Conversely, BCAA removal at both adsorbers was only minor. As a result, Fischer's Index showed a significant increase in the processed plasma, which became even more pronounced with increasing treatment duration. CONCLUSIONS: MARS enables an elevation of a pathologically decreased Fischer's Index as well as a reduction of systemic tryptophan levels in patients with liver failure. The effects of MARS on plasma amino acid dysbalance may contribute to an improvement of hepatic encephalopathy.

Amino Acids↗

Albumin dialysis: single pass vs. recirculation (MARS).

The single pass albumin dialysis (SPAD) was reported to be an alternative to the Molecular Adsorbent Recirculating System (MARS) for the effective removal of protein bound substances in liver failure. Three SPAD experiments using different albumin concentrations and dialysate flow rates were performed. In each experiment, 1000 ml human donor plasma, spiked with 250 mg unconjugated bilirubin, 200 mg sulfobromophthalein (BSP) and 115 mg glycocholic acid (N-[3alpha,7alpha,12alpha-trihydroxy-24-oxycholan-24-yl]glycine) - a conjugated bile acid (BA), circulated in a closed loop with 150 ml/min and was dialysed against albumin solution. These substances are bound to the different binding sites of albumin and have different association constants. For the comparison, the standard MARS experiment was performed using the same plasma flow rate of 150 ml/min. Moreover, the clearances of bilirubin for MARS and SPAD during clinical treatments were calculated using own data and those reported by Seige, Kreymann, Jeschke, et al. in Transplant Proc 1999; 31: 1371-5. The concentrations of bilirubin, BSP and BA were measured in plasma and dialysate and for these substances clearances (Cl) were calculated. It is known that the elimination rate of bilirubin is not very high during albumin dialysis in comparison to other substances, like bile acids, due to the high association constant. An increase of albumin concentration or the flow rate improved the efficacy but also raised the costs substantially. In this study, we have shown that MARS is the more effective kind of albumin dialysis for the important substances like bile acids. By SPAD an improvement of efficacy can be reached only by dramatic increase of the costs. Also, the earlier experiments showed that MARS is safer because of the removal of the stabilizers, which are normally included in the commercial albumin solutions.

Bile Acids and Salts↗

Postnatal pre- and postexposure passive immunization strategies: protection of neonatal macaques against oral simian-human immunodeficiency virus challenge.

Simian-human immunodeficiency viruses (SHIV) allow the evaluation of antiviral strategies that target the envelope glycoproteins of the human immunodeficiency virus 1 (HIV-1) in macaques. We previously protected neonates from oral challenge with cell-free SHIV-vpu+ by passive immunization with synergistic human neutralizing monoclonal antibodies (mAbs) (Baba et al., Nat Med 6:200-206, 2000). mAbs were administered prenatally to pregnant dams and postnatally to the neonates. Here, we used solely postnatal or postexposure mAb treatment, thus significantly reducing the amount of mAbs necessary. All neonatal monkeys were also protected with these abbreviated mAb regimens. Our results are directly relevant for humans because we used mAbs that target HIV-1 envelope glycoproteins. Thus, the large-scale use of passive immunization with neutralizing mAbs may be feasible in human neonates. The mAbs, being natural human proteins, can be expected to have low toxicity. Passive immunization has promise to prevent intrapartum as well as milk-borne virus transmission from HIV-1-infected women to their infants.

Administration, Oral↗

[Vascular dementia].

The past decade has seen a renewed interest in vascular dementia. The search for a causal relationship between a vascular event or a vascular cerebral lesion and dementia has led to new classification schemes which no longer consider vascular dementia a homogeneous entity but acknowledge the diversity of the clinical and morphological substrates of this syndrome. Deviation from the term "multi-infarct dementia" is only one but many consequencies of these recent developments. Etiologically, vascular dementia may result from cerebral small vessel disease leading to extensive leucencephalopathy or lacunes or may be the consequence of strategically located infarcts or multiple infarcts in large vessel territories. It may also be the consequence of global cerebral hypoperfusion, intracerebral hemorrhage or other mechanisms such as vasculitis. There is no definitive medical or surgical treatment for vascular dementia. Thus, it appears that stroke prevention offers the most immediate and substantial solution to reduce the morbidity and mortality. This is best substantiated for treatment of arterial hypertension. Once vascular dementia occurs control of vascular risk factors may be useful but this contention will require larger scale studies to provide more definite proof. A number of metabolically active drugs has been used for the treatment of cognitive symptoms in vascular dementia. Yet, the data are conflicting und the effects described modest at most. There is epidemiological evidence for a more than incidental co-existence between vascular and primary degenerative dementia which suggests that therapies found to be effective in Alzheimer's disease may also prove beneficial at least in subgroups of vascular dementia. Lately, this concept is tested by several studies on the efficacy of acetylcholinesterase inhibitors in vascular dementia.

Aged↗

B group vitamins and cleft lip and cleft palate.

B group vitamins including folic acid supplementation during pregnancy have been shown to be effective in preventing cleft lip and palate (CLP) in humans. The clinical trials for the prevention of malformation have been mostly empirically based. The aim of the present study was directed toward the elucidation of the mechanisms underlying the preventive measures. The teratogenic potency of vitamin deficiency over the whole period of gestation (days 1-18) and of food restriction during the critical period of palatogenesis (days 12 and 13) were investigated in the genetically different strains of NMRI and A/WySn mice. Furthermore the potential benefit of vitamin B supplementation/treatment in the genetically susceptible CLP strain was demonstrated for comparison with former work on a teratogenetically induced cleft palate model. The results illustrate the higher susceptibility of the NMRI strain to the teratogenic action of deficiency (increase of the CP rate from 3.8% to 25%) in contrast to A/WySn mice, which actually have a high spontaneous but relative teratogenic-resistant clefting rate (28-44%). A deficiency of each of the individual B vitamins is teratogenic, however total B group deficiency has the strongest effect in the case of deficiency of all B vitamins. This produces up to 25% cleft palates in the NMRI strain. Alternatively, vitamin B group treatment in pregnant A/WySn mice did not substantially influence the clefting rate in contrast to our former experience in Halle:AB mice. The results may help to elucidate the interplay of genetic conditions and exogenous (nutritional) factors in both the aetiology and prevention of CLP. This may further clarify the role of the B vitamins in empiric preventive clinical trials.

Animals↗

Rivastigmine in outpatient services: experience of 114 neurologists in Austria.

We performed an open-label study in Alzheimer patients on the use of rivastigmine in clinical routine. We evaluated the mode of dosing, safety and response to treatment over 24 weeks in 529 Alzheimer patients recruited by 114 neurologists. At the start of the study, and after 12 and 24 weeks, the participants were tested with the Mini-Mental State Examination and the Global Deterioration Scale. Titration of rivastigmine was slower than expected: After 2 weeks, only 41.8% of subjects received an effective daily dose of at least 6 mg. A total of 33.8% of patients experienced 305 mostly transient adverse events of mild or moderate intensity. Gastrointestinal symptoms occurred in 30.4% of subjects and symptoms of the nervous system in 16.4%. Similar to controlled trials, the cognitive performance of patients improved, with more than 60% of subjects showing improvement from baseline on the Mini-Mental State Examination by week 24. More than 40% of patients showed improvement on the Global Deterioration Scale. This study suggests that, in daily clinical practice, titration of rivastigmine deviates from the prescribing information. Under routine conditions, the safety profile of the drug is favourable, as is the response to treatment.

Aged↗

Empirical description and Monte Carlo simulation of fast neutron pencil beams as basis of a treatment planning system.

The fast neutron beam, used for fast neutron therapy in Essen, is produced by the nuclear reaction of a 14 MeV cyclotron-based deuteron beam on a thick beryllium target. The resulting neutron beam has a continuous energy spectrum with a mean and a maximum energy equal to 5.5 and 18 MeV, respectively. The dose delivered to the patient is computed by a treatment planning system (TPS) based on an empirical model, in which the dose components (neutron and photon) are described by analytical functions. In order to improve the dose calculation, and thus to use the fast neutron beam for other applications (e.g., Boron Neutron Capture Enhancement of Fast Neutron Therapy), in this work we aim to develop a new TPS. For this purpose, a model based on pencil beams of mono-energetic neutrons has been created. The neutron energy ranged from 0.25 MeV up to 17.25 MeV by steps of 0.5 MeV in order to cover the energy range of the Essen facility. The Monte Carlo method was then used to simulate the transport of neutrons within such pencil beams in a homogeneous water phantom. By using Monte Carlo techniques, it is possible to distinguish the energy deposition due to a primary collision in water to that due to scattered neutrons. The energy deposition due to pencil beams of 2.224 MeV photons, coming from hydrogen neutron capture reaction in the phantom or in the collimator, was also determined. In order to complete this work, air filled cylinders have been introduced in the water phantom. It is shown that the resulting depth dose curves for primary neutrons can be easily derived using the homogeneous phantom, and that the description of the effect on scattered neutron dose distribution is more complex. In this work we demonstrate the relevance of Monte Carlo simulations of mono-energetic neutron pencil beams for purposes of neutron treatment planning. Some additional work is still required to describe a clinical situation (continuous energy neutron spectrum) as well as to experimentally validate the method described here.

Adipose Tissue↗

Altered fatty acid composition of lung surfactant phospholipids in interstitial lung disease.

Deterioration of pulmonary surfactant function has been reported in interstitial lung disease; however, the molecular basis is presently unclear. We analyzed fatty acid (FA) profiles of several surfactant phospholipid classes isolated from large-surfactant aggregates of patients with idiopathic pulmonary fibrosis (IPF; n = 12), hypersensitivity pneumonitis (n = 5), and sarcoidosis (n = 12). Eight healthy individuals served as controls. The relative content of palmitic acid in phosphatidylcholine was significantly reduced in IPF (66.8 +/- 2.5%; means +/- SE; P < 0.01) but not in hypersensitivity pneumonitis (78.5 +/- 1.8%) and sarcoidosis (78.2 +/- 3.1%; control 80.1 +/- 0.7%). In addition, the phosphatidylglycerol FA profile was significantly altered in the IPF patients, with a lower relative content of its major FA, oleic acid, at the expense of saturated FA. In the phosphatidylcholine class, a significant correlation between the impairment of biophysical surfactant function and decreased percentages of palmitic acid was noted. We conclude that significant alterations in the FA profile of pulmonary surfactant phospholipids occur predominantly in IPF and may contribute to the disturbances of alveolar surface activity in this disease.

Adult↗

Innervation territories of mechano-insensitive C nociceptors in human skin.

Microneurographic recordings were obtained in the peroneal nerve from 20 mechano-insensitive units (CMi) and six mechano-heat responsive C units (CMH) in healthy human subjects. Their innervation territories in the skin of the leg or foot were assessed by transcutaneous electrical stimulation with a pointed probe at intensities of 10 to 100 mA (0.2 ms) and, when applicable, by mechanical von Frey hair stimulation. Electro-receptive fields (eRFs) of CMH units had a median area of 1.95 cm(2) when mapped with 10 mA that coincided approximately with mechano-receptive fields (mRFs) as mapped with a 750-mN von Frey hair. Fifty-milliampere stimuli increased the eRFs to 3.08 cm(2) in a concentric manner. This was probably due to current spread since these units are known to have low electrical thresholds. Further increase of the stimulus strength to 70 or 100 mA increased the eRFs only marginally. Mechano-insensitive units had much smaller eRFs (median: 0.35 cm(2)) than CMH units when mapped with the same pointed probe at 10 mA (n = 13). The receptive territories consisted of one distinct spot or of several spots separated by distances of more than 1 cm. However, when mapping stimuli of 50 mA were applied, eRFs became continuous and grew to a median area of 5.34 cm(2), i.e., larger than those of CMHs. The borders of eRFs of CMi units were significantly more irregular compared with CMH units. A further increase of the stimulus intensity to a maximum of 100 mA only marginally enlarged the eRFs. The CMi units could be activated by heat or chemical substances applied inside the 50-mA eRF, indicating that receptive nerve endings were mapped. Responsiveness to these stimuli was inhomogeneous within the eRFs. It was concluded that innervation territories of CMi units in human skin exceed those of CMH units in size by a factor of approximately 3. The widely branched terminals underlying the large fields are consistent with a role of this nociceptor class in axon reflex flare and preclude a role in exact spatial discrimination of noxious stimuli.

Adult↗

CT and MRI rating of white matter lesions.

Rating scales play an important role in the evaluation of computed tomography (CT) or magnetic resonance-detected white matter lesions (WML). Unfortunately, this type of visual semiquantitative assessment is not yet an optimal tool because commonly agreed concepts regarding its use are lacking. To generate a discussion platform for further improvement of CT and MRI rating, we will provide some basic definitions, summarize the advantages and disadvantages of scoring schemes and review current efforts towards the improvement of this tool. Future research will have to concentrate on deepening our understanding of the histopathologic substrates of WML and on strategies to document their progression.

Aged↗