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Biomedical subjects

H Schmidt

Publications and source records attributed to H Schmidt.

At least 325 records · Page 18Linked to original sources
PubMed1998

Effect of surface modifications of intraocular lenses on the adherence of Staphylococcus epidermidis.

The development of polymers with different surface properties and surface modifications of intraocular lenses (IOL) should reduce foreign body reactions after implantation by reducing the surface hydrophobicity of the lenses. It was examined how far such surface variations influenced the adhesiveness of bacteria. The most common organism isolated from cases of postoperative endophthalmitis is Staphylococcus epidermidis. For this reason, three strains of this species, the type strain ATCC 14990 and two clinical isolates (8687, 6579 I), with different hydrophobic surfaces, were studied. IOL made of PMMA, silicone, and a copolymer as well as PMMA lenses with modified surfaces (unpolished, polished, silanized, and heparinized) were used. Bacteria were radiolabelled with 3H-thymidine and the adherent bacteria were calculated per mm2 of lens surface. The three strains adhered better to the unpolished surface of silicone than to PMMA. Treatment of PMMA surface by polishing diminished the differences between the strains. An influence of hydrophobic interactions on the adherence of S. epidermidis ATCC 14990 was demonstrated. The adherence of this hydrophobic type strain was clearly reduced by heparinization of the PMMA surface. In contrast, the hydrophilic catheter isolate 6579 I adhered better to modified surfaces. This strain differed clearly in its PFGE pattern from both hydrophobic strains. Hydrophobic interactions play a role in the bacterial adherence to intraocular lenses in vitro and in vivo. Modifications of polymer surfaces, however, can result in rather different effects depending on the bacterial surface composition and properties.

Bacterial Adhesion↗
PubMed1998

Heat shock protein (hsp70) in brown trout epidermis after sudden temperature rise.

So far, hsp70 has not yet been studied in the fish skin. This organ has a potential as an indicator organ and we investigate whether hsp70 could be used as a biomarker. In this study, we examined whether and how the epidermis reacts to a temperature rise. Brown trout, Salmo trutta fario, were exposed to higher temperature for 2 h and were allowed to recover subsequently. Samples were taken from controls, after heat shock, as well as after 24 and 48 h of recovery. The occurrence of hsp70 in trout skin was examined by Western blot. The amount of hsp70 was higher after 2-h heat shock and was rising until the end of the experiment. Immunocytochemically, hsp70 was detected in epidermal filament cells. After 2-h heat shock, hsp70 was predominantly located in the nucleus. At this time, light and electron microscopy revealed several features known to occur under a variety of stressors. Ultrastructurally, the appearance of compact filament aggregates in pavement cells was remarkable. After 24 h of recovery, filament compaction was lacking and after 48 h aspects of regeneration were obvious. However, an increased amount of apoptotic cells in the epidermis was prominent at this time only.

Animals↗
PubMed1998

Long-chain polyunsaturated fatty acids in plasma and erythrocyte membrane lipids of children with phenylketonuria after controlled linoleic acid intake.

It has been reported that children with classical phenylketonuria (PKU) have reduced levels of arachidonic acid (AA, 20:4 n-6) and docosahexaenoic acid (DHA, 22:6 n-3) in plasma and membrane phospholipids compared to controls and may therefore require supplementation. However, it is not established that these changes are specific for PKU. They may as well be attributed to the specific composition of a largely vegetarian diet used for dietary PKU treatment. We therefore investigated the fatty acid composition of plasma phospholipids (PL), plasma cholesterol esters (CE), red blood cell phosphatidylcholine (PC), and red blood cell phosphatidylethanolamine (PE) in two groups of PKU patients including 8 children between 1 and 6 years (group A), 9 adolescents between 11 and 18 years (group B), and 20 age-matched healthy controls. Group A had good dietary control (median plasma phenylalanine 272 mumol/L during the last 6 months before phospholipid analysis) while median phenylalanine in group B was 714 mumol/L (p < 0.001). When compared to age-matched controls, group A showed significantly lower DHA levels in PE (4.21 vs 5.85 weight% (wt%), p < 0.01), in PC (1.02 vs 1.25 wt%, p < 0.05) and in CE (0.25 vs 0.54 wt%, p < 0.05). There was no significant difference of DHA between group B and controls. AA levels were similar in phospholipids of all groups. We conclude that reduced levels of long-chain polyunsaturated fatty acids in PKU patients occur only in those patients with strict dietary therapy with respect to n-3 fatty acids, most probably caused by reduced intake of n-3 fatty acids.

Adolescent↗
PubMed1998

Pharmacokinetics of intravenous busulfan and evaluation of the bioavailability of the oral formulation in conditioning for haematopoietic stem cell transplantation.

Busulfan (BU) is included in many conditioning protocols for haematopoietic stem cell transplantation (HSCT). Pharmacokinetic parameters in individual patients have been related to short-term toxicity and risk of relapse after HSCT. In a series of 11 patients receiving the usual 16 x 1 mg/kg schedule over 4 days, we investigated the pharmacokinetics of replacing one dose with an intravenous formulation (BU in DMSO) which we had previously investigated in dogs. A dose of 0.5-0.6 mg/kg was used. No acute side-effects of BU/DMSO infusions administered over 1 h were observed. Bioavailability of BU powder capsules was on average 70% (range, 44-94%). Interindividual variability of the resulting AUC after intravenous doses was still substantial. Further studies are under way to define the possible role of BU/DMSO infusions in conditioning before HSCT.

Administration, Oral↗
PubMed1998

When should prophylactic treatment in patients with haemophilia A and B start?--The German experience.

Radiological and orthopaedic outcome in severe and moderate haemophilia A and B patients undergoing long-term prophylactic treatment were prospectively investigated focusing on the age of onset of prophylaxis and the number of joint bleedings prior to treatment. We report on 21 patients with severe and moderate haemophilia A and B receiving prophylactic treatment of between 3.1 and 16.1 years' duration. Three patient groups were evaluated according to the age at onset of prophylaxis. In group I prophylactic treatment was initiated in the first 2 years of life. Patients in group II received prophylaxis at the age of 3-6 years. Late-onset or secondary prophylactic treatment was started at the age of 6 years and above in seven patients (group III). All patients received virus-inactivated F VIII or F IX concentrates at dosages of 30-50 IU/kg body weight i.v. three times per week for those with haemophilia A and twice per week for those with haemophilia B. Elbow, knee and ankle joints were investigated at 3-4-yearly intervals according to the radiological and orthopaedic scores recommended by the World Federation of Haemophilia. The total number of joint bleedings before and after start of prophylaxis were recorded in all patients. In group I 7/8 patients had unaffected joints with constant radiological and orthopaedic scores of zero or 1, after a median of 11.25 years of prophylactic treatment. One patient in this group demonstrated mild radiological alterations (score 4). Patients in group II showed neither radiological nor orthopaedic alterations at study entry. Surprisingly, worsening joint scores could be detected despite ongoing prophylaxis after the 3-year interval (median orthopaedic score 4, median radiological score 8). Treatment group III already showed considerable joint damage at study entry with a median radiological score of 11 (0-33) and a median orthopaedic score of 4 (0-11). Despite prophylactic treatment, both radiological (median 19.5, range 2-47) and orthopaedic scores (median 8, range 2-12) deteriorated after 3 years. Prior to onset of prophylaxis, no or only one joint bleeding occurred in treatment group I. In group II, a median of six joint bleeds (range 1-8) was reported before prophylaxis was started. Patients in group III usually experienced a median of more than 10 joint haemorrhages (range 6-10 or more). Under prophylactic treatment the number of joint bleedings decreased significantly in groups II and III. However, radiological and orthopaedic scores increased as a sign of progressing osteoarthropathic alterations in patients reporting more than five joint haemorrhages onset of prophylaxis whereas no joint alterations could be assessed in patients with no or only one joint bleeding episode prior to prophylaxis. Even a small number of joint bleedings seems to cause irreversible osteoarthropathic alterations leading to haemophilic arthropathy. Once apparent, further progression of joint damage could not be arrested despite of prophylactic treatment (groups II and III). In order to prevent haemophilic arthropathy, effective prophylaxis should be started before or at least after the first joint bleeding in severe haemophilia A and B.

Adolescent↗
PubMed1998

Identification of a novel delta 6-acyl-group desaturase by targeted gene disruption in Physcomitrella patens.

The moss Physcomitrella patens contains high levels of arachidonic acid. For its synthesis from linoleic acid by desaturation and elongation, novel delta 5- and delta 6-desaturases are required. To isolate one of these, PCR-based cloning was used, and resulted in the isolation of a full-length cDNA coding for a putatively new desaturase. The deduced amino acid sequence has three domains: a N-terminal segment of about 100 amino acids, with no similarity to any sequence in the data banks, followed by a cytochrome b5-related region and a C-terminal sequence with low similarity (27% identify) to acyl-lipid desaturases. To elucidate the function of this protein, we disrupted its gene by transforming P. patens with the corresponding linear genomic sequence, into which a positive selection marker had been inserted. The molecular analysis of five transformed lines showed that the selection cartridge had been inserted into the corresponding genomic locus of all five lines. The gene disruption resulted in a dramatic alteration of the fatty acid pattern in the knockout plants. The large increase in linoleic acid and the concomitant disappearance of gamma-linolenic and arachidonic acid in all knockout lines suggested that the new cDNA coded for a delta 6-desaturase. This was confirmed by expression of the cDNA in yeast and analysis of the resultant fatty acids by GC-MS. Only the transformed yeast cells were able to introduce a further double bond into the delta 6-position of unsaturated fatty acids. To our knowledge, this is the first report of a successful gene disruption in a multicellular plant resulting in a specific biochemical phenotype.

Amino Acid Sequence↗
PubMed1998

Immunocytochemical localization of somatostatin receptor sst2A in the rat spinal cord and dorsal root ganglia.

Intrathecal administration of octreotide, a stable somatostatin analogue, provides pain relief in patients, and locally applied somatostatin inhibits firing of nociceptive dorsal horn neurons. In the present study, we have raised polyclonal antibodies that specifically detect the somatostatin receptor sst2A and used these antisera for immunocytochemical localization of the receptor protein in the rat spinal cord and dorsal root ganglia. In the superficial layers of the dorsal horn, sst2A-like immunoreactivity (Li) formed a dense network consisting of neuronal perikarya and dendrites which were often closely apposed by, but not co-contained within, somatostatin-14-immunoreactive nerve fibres and terminals. sst2A-Li was resistant to dorsal rhizotomy and did not colocalize with either substance P or calcitonin gene-related peptide suggesting that sst2A-Li was not located to primary afferents, but rather confined to second-order spinal neurons. The position of sst2A-Li perikarya and dendrites in the dorsal horn appeared to be similar to those containing mu-opioid receptor-Li; however, double labelling experiments revealed no instances of coexistence of these two receptors. sst2A-Li was also observed in the dorsal root ganglia predominantly targeted to the somatic plasmalemma of medium size neurons distinct from those expressing somatostatin-14 or delta-opioid receptors. Thus, the present results not only provide a morphological substrate for spinal octreotide analgesia but also show that somatostatin and opioids are poised to modulate nociceptive transmission by distinct anatomical systems.

Amino Acid Sequence↗
PubMed1998

Characterization of epidermal wound healing in a human skin organ culture model: acceleration by transplanted keratinocytes.

Few data are available on early regeneration of human epidermis in vivo. We have established a supravital skin organ culture model for epidermal wound healing by setting a central defect (3 mm diameter) in freshly excised skin specimens and culturing under air exposure. Re-epithelialization was followed for up to 7 d by histology and immunohistologic analysis of various markers for differentiation and proliferation. In 12 of 19 cases (63%; 5% fetal calf serum) or six of 21 cases (29%; 2% fetal calf serum), the wounds were re-epithelialized spontaneously after 7 d. After transplantation to the wounds of 1-2 x 10(6) dissociated allogenic cultured epidermal or about 1 x 10(6) autologous outer root sheath keratinocytes, 18 of 21 cases (86%; 5% fetal calf serum) or 17 of 21 cases (81%; 2% fetal calf serum) were healed within the same period. Histologically, early neoepithelium (3 d) was disordered after keratinocyte transplantation, whereas later (7 d) it had gained a more ordered stratification, exhibiting a thin discontinuous granular and a compact horny layer. At this stage, not only hyperproliferative (CK 6) but also, abundantly, maturation-associated cytokeratins (CK 1, CK 10) were detected immunohistochemically. Analyses of regenerated epidermis after transplantation of (i) keratinocytes labeled in vitro with BrdU and (ii) heterosexual keratinocytes by immunohistochemistry and fluorescence in situ hybridization for the Y chromosome, respectively, clearly showed that external keratinocytes are physically integrated into the regenerated epidermis and extendedly contribute to its formation. The data presented here demonstrate improvement and acceleration of epidermal re-epithelialization by transplantation of keratinocytes.

Adolescent↗
PubMed1998

[Economic aspects of anesthesia. II. Cost control in clinical anesthesia].

The primary scope of economic analyses is the quantification of the costs (input) in relation to the results (outcome, output). According to whether a similar or different dimension of outcome parameters is chosen, it is possible to differentiate between cost minimisation, cost effectiveness, cost benefit and cost utility analyses. Decision trees and sensitivity analyses serve to develop or examine cost outcome studies. The principal perspective of economic analysis is of crucial significance. In the present overview of cost control programmes in clinical anaesthesia, the perspective chosen throughout is that of budget responsibility in a department of anaesthesiology. With regard to economic factors in clinical anaesthesiology, the cost of medical and nursing staff represents the largest cost block. It is, therefore, essential that personnel is efficiently employed, i.e. how the perioperative procedure is organised. In the area of material costs, blood products--including coagulation factors and plasma substitutes--are particularly cost intensive, followed by medical products and drugs, especially muscle relaxants and inhalational anaesthetics. In the perioperative context, the costs of anaesthesia personnel account for 5-15% of the total costs of patient care, while material costs account for 2-10%. In view of this small portion of the total costs, cost control programmes in anaesthesia can only make a relatively small contribution to reducing overall cost. However, it must be realised that anaesthesia care is vitally important for the perioperative process which means that in this context cost-effectiveness interventions have consequences that also affect other fields, e.g. postoperative pain service besides anaesthesia. In conducting economic analyses, cost considerations or reductions cannot be targeted alone, but must always also integrate outcome aspects so that costs and quality are regarded in relation to one another.

Anesthesia↗
PubMed1998

A European multicenter study of phenylalanine hydroxylase deficiency: classification of 105 mutations and a general system for genotype-based prediction of metabolic phenotype.

Phenylketonuria (PKU) and mild hyperphenylalaninemia (MHP) are allelic disorders caused by mutations in the gene encoding phenylalanine hydroxylase (PAH). Previous studies have suggested that the highly variable metabolic phenotypes of PAH deficiency correlate with PAH genotypes. We identified both causative mutations in 686 patients from seven European centers. On the basis of the phenotypic characteristics of 297 functionally hemizygous patients, 105 of the mutations were assigned to one of four arbitrary phenotype categories. We proposed and tested a simple model for correlation between genotype and phenotypic outcome. The observed phenotype matched the predicted phenotype in 79% of the cases, and in only 5 of 184 patients was the observed phenotype more than one category away from that expected. Among the seven contributing centers, the proportion of patients for whom the observed phenotype did not match the predicted phenotype was 4%-23% (P<.0001), suggesting that differences in methods used for mutation detection or phenotype classification may account for a considerable proportion of genotype-phenotype inconsistencies. Our data indicate that the PAH-mutation genotype is the main determinant of metabolic phenotype in most patients with PAH deficiency. In the present study, the classification of 105 PAH mutations may allow the prediction of the biochemical phenotype in >10,000 genotypes, which may be useful for the management of hyperphenylalaninemia in newborns.

Alleles↗
PubMed1998

Contribution of overproduced chromosomal beta-lactamase and defective outer membrane porins to resistance to extended-spectrum beta-lactam antibiotics in Serratia marcescens.

Using clinical strains of Serratia marcescens with low and high resistance to extended-spectrum beta-lactam antibiotics, the relative contribution of chromosomal beta-lactamase and defective outer membrane porins to resistance was determined. Low-level resistance was caused by overproduced beta-lactamase alone. High-level resistance was due to beta-lactamase overproduction and defects of porin OmpF or OmpF and OmpC. Overproduction of beta-lactamase in bacteria with both degrees of resistance was eliminated by transformation with cloned ampD+, the gene (from Escherichia coli) for negative modulation of beta-lactamase induction. In transformants of highly resistant bacteria with normally low and inducible beta-lactamase production, the remaining porin defects alone imparted only minimal resistance to extended-spectrum beta-lactam antibiotics.

Bacterial Proteins↗
PubMed1998

Antiendothelial cell antibodies in thromboangiitis obliterans.

The occurrence of autoimmune phenomena in 28 patients with thromboangiitis obliterans (Buerger's disease) was determined. The following were sought: antineutrophil cytoplasmic antibodies against proteinase 3 (cANCA) and myeloperoxidase (pANCA), antinuclear antibodies, anti-Ro antibodies, anticardiolipin antibodies, and antiendothelial cell antibodies (AECA). For the last, an enzyme-linked immunosorbent assay was developed which verified the presence of the AECA phenomenon with immunofluorescence and confocal microscopy. Seven patients with active disease had AECA titers of 1,857 +/- 450 arbitrary units (AU) compared with 126 +/- 15 AU in 30 normal control subjects (P < 0.001) and 461 +/- 41 AU in 21 patients in remission (P < 0.01). Antibodies from the sera of patients with active disease reacted not only with surface epitopes but also with sites within the cytoplasm of human endothelial cells. AECA may be useful in following disease activity and may play a role in the pathogenesis of thromboangiitis obliterans.

Adult↗
PubMed1998

Integrating the teaching of basic sciences, clinical sciences, and biopsychosocial issues.

In this chapter, the author describes integrating the teaching of the basic sciences, clinical sciences, and biopsychosocial issues in medical education as part of the curricular reform efforts initiated by schools that participated in The Robert Wood Johnson Foundation's project "Preparing: Physicians for the Future: Program in Medical Education." The author focuses on the approaches the eight schools adopted, the challenges they encountered, and the lessons they learned in attempting to implement more integrated curricula. Integration was promoted both within and among various components of medical education. For example, in some cases discipline-based courses in the basic sciences were replaced with interdisciplinary courses. Further, efforts were made both to bring clinical relevance to the basic sciences and to strengthen basic science in the clinical years. All the schools also promoted the study of the humanities and biopsychosocial sciences throughout the curriculum. The author describes problems encountered in these endeavors, resources needed to support interdisciplinary courses, the benefits of integration, and common lessons learned by the eight schools.

Biology↗
PubMed1998

Dopexamine attenuates endotoxin-induced microcirculatory changes in rat mesentery: role of beta2 adrenoceptors.

OBJECTIVE: To investigate the influence of dopexamine on endotoxin-induced leukocyte adherence and on vascular permeability in postcapillary venules of rat mesentery. DESIGN: Randomized, controlled trial. SETTING: Experimental laboratory. SUBJECTS: Twenty-seven male Wistar rats, weighing 250 to 350 g. INTERVENTIONS: Rats received one of three treatments: a) infusion of Escherichia coli endotoxin without dopexamine pretreatment; b) infusion of endotoxin with dopexamine pretreatment; or c) infusion of endotoxin after pretreatment with dopexamine and ICI 118,551, a selective beta2-receptor antagonist. MEASUREMENTS AND MAIN RESULTS: Leukocyte adherence, red blood cell velocity, and vessel diameters in postcapillary venules were evaluated using in vivo videomicroscopy. Vascular permeability was determined by measuring the extravasation of fluorescence-labeled albumin. Venular wall shear rate was calculated from red cell velocity and vessel diameter. Dopexamine attenuated both the increase in leukocyte adherence and vascular permeability during endotoxemia. The attenuating effect on leukocyte adherence could not be antagonized by the beta2-adrenoceptor antagonist. However, the attenuating effect on vascular permeability was antagonized by ICI 118,551. Dopexamine prevented a decrease in venular wall shear rate during endotoxemia. This effect was not influenced by ICI 118,551. CONCLUSIONS: Dopexamine attenuates endotoxin-induced microcirculatory disturbances in rat mesentery. The attenuating effect on vascular permeability is a beta2-adrenoceptor-mediated process, whereas the beta2-adrenoceptor actions of dopexamine play no significant role in attenuating leukocyte adherence.

Adrenergic beta-Agonists↗
PubMed1998

The inflammatory cytokine response after autotransfusion of shed mediastinal blood.

BACKGROUND: The inflammatory response in patients undergoing cardiac surgery with cardiopulmonary bypass is well known and increased levels of inflammatory cytokines have been shown. High levels of cytokines have been reported in blood drained from the surgical field. The present study aimed to elucidate whether autotransfusion of shed mediastinal blood in itself causes increased cytokine levels in coronary artery bypass graft (CABG) patients. METHODS: A prospective, randomized controlled study was performed in 23 patients having elective uncomplicated CABG. Autotransfusion of shed mediastinal blood was done every hour for 18 h in group I. In group II, the shed mediastinal blood was accumulated for 4 h in the cardiotomy reservoir and then autotransfused every hour for the next 14 h. Plasma levels of tumour necrosis factor-alpha (TNFalpha) and interleukin (IL)-1alpha, IL-1beta, IL-6 were measured. In vitro study of cytokine production was performed with or without stimulation (phytohaemagglutinin (PHA) and Escherichia coli (E. coli) lipopolysaccharide (LPS)). RESULTS: We found high levels of IL-6 in the shed mediastinal blood. However, autotransfusion of shed mediastinal blood did not lead to increased level of cytokines (TNFalpha, IL-1alpha, IL-1beta and IL-6) in plasma in group I nor in group II. In vitro study showed activation of the leucocytes in the shed mediastinal blood with a significantly increased production of TNFalpha and IL-6 both in the stimulated and non-stimulated samples. CONCLUSION: Shed mediastinal blood contains high levels of IL-6. However, autotransfusion of shed mediastinal does not cause measurable elevations in plasma levels of IL-6. In vitro study shows that autotransfusion activates leucocytes, which may enhance production of inflammatory cytokines.

Adult↗
PubMed1998

Plasma antioxidants and cognitive performance in middle-aged and older adults: results of the Austrian Stroke Prevention Study.

OBJECTIVES: To study the association between cognitive status and plasma concentrations of various antioxidants in middle-aged and older individuals without neuropsychiatric disease. DESIGN: Evaluation of cross-sectional data from a cohort study. SETTING: The Austrian Stroke Prevention Study. PARTICIPANTS: A total of 1769 subjects aged 50 to 75 years, with no history or signs of neuropsychiatric disease, selected randomly from the community register. MEASUREMENTS: The score on the Mattis Dementia Rating Scale (MDRS) was dichotomized according to age-and education-specific lowest quartile cut-off points. Reversed-phase high performance liquid chromatography measurements of the plasma concentrations of lutein/zeaxanthin, cryptoxanthin, canthaxanthin, lycopene, alpha-carotene, beta-carotene, retinol, gamma-tocopherol, alpha-tocopherol, and ascorbate were measured. RESULTS: Individuals with MDRS results below the lowest quartile cut-off point had lower levels of beta-carotene and alpha-tocopherol than their counterparts with test performance above this limit (0.44+/-.33 micromol/L vs 0.51+/-.48 micromol/L, P < .001; and 29.50+/-7.98 micromol/L vs 30.93+/-11.10 micromol/L, P < .001, respectively). Only alphatocopherol remained significantly associated with cognitive functioning when logistic regression analysis was used to adjust for possible confounders including age, sex, month of blood sampling, years of education, smoking, lipid status, and major risk factors for stroke (P = .019). CONCLUSION: These observations are compatible with the view that some dietary antioxidants may protect against cognitive impairment in older people.

Age Factors↗