Biomedical subjects
Publications and source records attributed to A Schmidt.
Technological advances are changing the way the world shares information and conducts daily business, CARING asked home care colleagues around the world to respond to a question about technology's role in home care delivery. Although the degree of technology's involvement differs from country to country, each country is aware of the possibilities and is looking toward the future.
Malassezia furfur is an anthropophilic fungus that belongs to the physiological skin flora. The fungus can grow in a yeast phase as well as in a mycelial phase; on nonaffected skin the fungus is mainly prevalent in the yeast phase. The organism has complex lipid requirements for growth, which also explains its occurrence on the skin. This also leads to the requirement for specially supplemented media for in vitro cultivation. Malassezia furfur is the causative agent of pityriasis versicolor. It also seems to be associated with seborrheic dermatitis and dandruff formation, folliculitis, confluent and reticulate papillomatosis, and the provocation of psoriatic lesions. Many substances for topical application, such as azole antimycotics, ciclopirox olamine, piroctone-olamine, zinc pyrithione, or sulfur-containing substances are effective in the treatment of these diseases. In recent years rare cases of systemic infections and fungemias caused by Malassezia have been reported.
A venous blood sample taken at autopsy cannot be considered to represent the antemortem blood concentration of a particular substance. Autolytic processes cause disintegration and increasing permeability of the physiological and anatomical barriers such as vascular walls and lead to changes in substance concentrations. In the present study, the experimental design represents an in vitro postmortem simulation of a drug substance crossing a venous wall. The postmortem behavior of morphine, morphine-3- and morphine-6-glucuronide was investigated. A Chien-Valia-diffusion chamber with a patch of inferior vena cava as diffusion barrier was used. For optimal simulation of postmortem events, vein sampling was restricted to selected autopsy cases. Parameters for the analysis of diffusion across the vascular tissue were dependence on time, temperature, and initial substance concentrations. The penetration behavior simulating venous efflux and influx of the substances was studied by different orientation of the venous wall in the experiments. Rhodamine B was used as a model substance to visualize the binding to the tissue and the passage across the venous wall. The permeation of morphine, morphine-3- and morphine-6-glucuronide across a vein tissue was found to be mainly dependent on the disintegration of the vascular wall and on the postmortem time period as well as on concentration gradients. From the data of this preliminary in vitro study, it can be concluded that a lag time for transvascular diffusion exists postmortem. However, it could be demonstrated, that adsorption to and penetration into the vascular tissue may alter intraluminal blood concentrations even at an early stage of the postmortem time period.
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BACKGROUND: Although chronic progressive renal transplant failure (CPTF) is one of the leading causes of end-stage renal disease its exact pathogenesis is still incompletely understood. Histopathological as well as clinical similarities between chronic native kidney diseases and CPTF open the possibility that the latter condition is not exclusively due to a prolonged immunological insult to the grafted organ but also is caused by a mismatch between the metabolic demands of the recipient and the excretory capacity of the transplanted kidney. In this retrospective study we defined clinical parameters which are associated with CPTF. METHODS: Creatinine clearance was followed in 469 patients 45 +/- 0.9 months after transplantation for 2 years. Various immunological and non-immunological parameters were included in an univariate and multivariate regression analysis to define those which are independently associated with CPTF, defined as a decrease of creatinine clearance during the study period. RESULTS: Of all the parameters proteinuria, systolic blood pressure, high Cyclosporin trough concentrations and the cumulative steroid dose were found to be significantly associated with CPTF. A persistent proteinuria of > 2 g/d during the observation period was found to have a positive predictive value of 83% for a deterioration of excretory kidney function of > or = 25% within 2 years. CONCLUSION: In CPTF immunological as well as non immunological factors are independently associated with the decline of excretory allograft function in the late postoperative period.
The development of central auditory functions in cochlear implant (CI) patients was studied over six months of rehabilitation. Examinations were performed beginning with the first week after processor calibration, and in monthly follow-up sessions thereafter. The subjects were given a simple auditory perception task (detection of a 400 Hz and a 1450 Hz tone), as well as an oddball-paradigm (detection of one of the tones as a rare deviant). Auditory evoked potentials, reaction time and errors were recorded. Results from five patients, two postlingually deaf and three prelingually deaf CI recipients are shown. Generally, in the auditory evoked potentials of patients a shortening of N100 latency towards those of subjects with normal hearing was seen from month to month. However, in the prelingually deaf patients this effect was weaker and more variable over time. Three CI recipients showed a P300 component in the oddball-paradigm in correlation with their performance. Two prelingually deaf patients failed to show a P300 in the oddball-paradigm. For both components, the N100 and the P300 we found a larger spreading over the skull in the patients compared to a normal hearing person. The results show that from the very first days after initial processor fitting prelingually and postlingually deaf CI recipients may show cortical correlates of stimulus processing and discrimination. For some components of the auditory evoked potentials an initial temporal change but a maintained larger spreading over the skull was seen.
At the time of ovulation the lining epithelium of the mammalian oviduct consists of columnar ciliated and secretory cells. These mature cells are dependent on ovarian steroids in carnivores. Oestradiol induces differentiation of these cells and maintains their mature functional state, and progesterone induces dedifferentiation. The secretory cells synthesize and secrete an oestrogen-dependent high molecular weight glycoprotein. The cDNAs encoding oviductal glycoproteins from several species have been sequenced and show high similarity. The human cDNA hybridized with a single message on northern blots of total oviduct RNA obtained from oestradiol-treated cats (about 2.3 kb) and dogs (about 2.1 kb). This glycoprotein is the major nonserum protein present in the oviductal lumen at the time of ovulation, fertilization and early embryonic development. The glycoproteins associate with the zona pellucida of oviductal eggs in all species studied to date. Recent studies suggest that the bovine glycoprotein facilitates sperm capacitation and significantly increases the ability of bovine spermatozoa to fertilize bovine oocytes in vitro, that the hamster glycoprotein increases the sperm penetration rate of the zona pellucida by three times and that the human glycoprotein increases sperm binding to the zona pellucida by three times. All of the evidence for a biological function for this glycoprotein is derived from studies performed in several different species at reproductive stages before fertilization. The biological actions of this glycoprotein suggest a potential role for the glycoprotein in fertility control. Specifically, purified or recombinant glycoprotein may improve success in IVF procedures by enhancing binding of spermatozoa to the zona pellucida and improving fertilization rates. The glycoprotein may also be a potential immunocontraceptive target since antibodies generated against the oviductal glycoprotein may prevent fertilization by preventing binding of spermatozoa to the zona pellucida.
Angiotensin converting enzyme (ACEi) inhibition retards renal function loss, but the therapeutic benefit varies between individuals. Renoprotection is poor in patients with the ACE DD genotype. ACE genotype is reported to affect short-term antiproteinuric response to ACEi, a predictor of long-term renoprotection, in some studies but not in others. Short-term responses to ACEi are enhanced by stimulating the renin-angiotensin system, that is, sodium restriction. We hypothesized that the ACE genotype influences sodium dependency of the response to ACEi. Therefore, we performed a cross sectional analysis of short-term responses to ACEi (enalapril or lisinopril) in 88 patients with stable non-diabetic proteinuria (> 1.0 g/day) and variable sodium intake. ACE genotype distribution was: DD, N = 25; ID, N = 40; II, N = 23. Baseline proteinuria (5.9 +/- 0.7; 5.8 +/- 0.07; 4.8 +/- 0.8 g/day, respectively) and mean arterial pressure (108 +/- 3; 106 +/- 2; 107 +/- 2 mm Hg, respectively) were similar for the three genotypes. ACEi similarly reduced proteinuria (-49 +/- 5; -55 +/- 4, -48 +/- 6%, respectively) and blood pressure (-12 +/- 3; -14 +/- 1 and -12 +/- 2%, respectively) in the three groups. Interestingly, the responses to ACEi of proteinuria (r = 0.42, P < 0.05) and blood pressure (r = 0.41, P < 0.05) correlated with urinary sodium excretion in DD genotype but not in the ID (r = 0.05 and 0.17, resp) or II genotype (r = 0.09 and 0.08, respectively). Thus, in the DD group, individuals with a high sodium excretion had a less effective response to ACEi. We conclude that differences in sodium status could account for disparities between studies on the relationship between ACE genotype and response to ACEi, and that sodium restriction might be a strategy to circumvent treatment resistance in the DD genotype.
PURPOSE: To compare the predictive accuracy for future ischemic events of heart rate limited treadmill exercise test (HET) and coronary angiography (CA) applied to survivors of an uncomplicated myocardial infarction. METHODS: 142 consecutive patients (55 +/- 11 years, 80% males), presenting a non complicated acute myocardial infarction (AMI) were included. HET was performed 10 +/- 3 days after AMI, and CA during hospital stay or within 4-6 weeks. HET positivity criteria were: 1) horizontal or down-sloping ST segment displacement > or = 1 mm; 2) angina; 3) arterial pressure drop during exercise; 4) low workload (< 6 METS); 5) complex ventricular arrhythmia. At CA lesions causing > or = 50% of luminal reduction were considered significant. HET and CA results were correlated to ischemic events occurring during the follow-up (unstable angina in 20%, cardiac death 6%, and reinfarction 6%). RESULTS: HET was positive in 69 (49%) patients, exhibiting a positive predictive value for ischemic events (PV+) of 26% and a negative predictive value (PV-) of 77%. The mean event-free time was 43 +/- 3 months for positive HET and 46 +/- 3 months for a negative one (p = 0.48). CA showed 0-1 vessel involvement in 93 (66%) patients and > or = 2 vessels in 49 (34%) patients. The presence of multivascular disease at CA presented a PV+ of 37% and PV- of 82%; the mean event-free time was 37 +/- 4 months for patients with multivascular involvement and 48 +/- 2 months for patients without this pattern (p = 0.007). CONCLUSION: The predictive accuracy of HET for future ischemic events in the thrombolytic era is markedly reduced. This population of AMI survivors presents an overall good prognosis that seems to justify the poor predictive accuracy of this test.
From 1988 through 1995 we operated 48 patients with dislocated humeral fractures using the T-Plate (median age 66 years [20 to 90 years], 32 male, 16 female). After a median 22 months (9 to 60 months) 33 patients were followed up clinically and radiologically. Six patients had suffered a 2-part fracture, 17 a 3-part fracture, and 10 a 4-part fracture. Judged by the Constant score 6 patients reached a very good result, 8 had a good result, 4 a satisfactory and 15 a poor result. Radiologically we saw an arthrosis in 31%, an axial deviation in 50%, and a dislocation of the fragments in 72%. The rate of necrosis of the humeral head was 39%. MRI (17 patients) provided additional relevant information about soft tissue and bone quality and is valuable in the early detection of necrosis of the humeral head. Functionally poor results correlated rather to dislocated fragments and persisting axial deviation than to the type of fracture or the necrosis of the humeral head. The T-plate osteosynthesis is one way to treat dislocated fractures of the proximal humerus, if early operation, correct reposition, and biological principles are respected.
Fungal vaginal infections/colonisations can be divided into a symptomatic vaginal candidiasis and an asymptomatic vaginal Candida-carriage. The latter seems to be a predisposing factor for the development of a symptomatic vaginal candidiasis. The fungal organism isolated most frequently is Candida albicans, followed by Candida glabrata, which was previously also known as Torulopsis glabrata. To a lower extend, other Candida species such as Candida tropicalis and Candida krusei can be prevalent in the vulvovaginal region. Predisposing factors for vaginal candidiasis are gravidity, diabetes mellitus or a therapy with immunosuppressive agents. Also gestagenes showed to be a pre-disposing factor for vaginal candidiasis. Divergent results concerning the predisposition to vaginal candidiasis or colonisation due to oral contraception have so far been reported. Therefore we performed a study with two healthy collectives of female volunteers (n = 2 x 60) which were different concerning the taking of oral contraceptives. Overall, in 17% of the subjects (20/120) yeast could be cultured out of the vaginal secretions. There was no evidence for a higher rate of Candida-colonisation in subjects taking oral contraceptives. Further, there was no evidence for a relationship between the length of the taking of oral contraceptives and the rate of vaginal yeast-carriage. Also the type of oral contraceptive (combination or sequential contraceptive) had no influence on the frequency of Candida-carriage. Candida albicans was the most prevalent yeast (16/20), followed by Candida glabrata (4/20).
The results of surgical treatment with tension band wiring versus conservative therapy with bandages are described in a retrospective study. Operative therapy is associated with complications in 32.3% and two occasions of hospitalisation. The advantages of conservative therapy are obvious: it is easy and comfortable for the patient; there are no complications and low costs, and it is associated with a shorter temporary disablement. Therefore, conservative therapy is our standard, and surgery is performed only for Rockwood IV-VI lesions and in exceptional cases.
The overall incidence of malignancy in renal transplant recipients is 100-fold higher compared with age matched controls. Routine clinical evaluation therefore often includes the determination of serum tumor markers AFP, CA19-9, CEA, CA125, CA15-3, PSA, and calcitonin. We evaluated the specificity and the sensitivity of these markers in 575 renal allograft recipients. Specificity varied between 0.69 (CA 125) and 0.96 (PSA) in 532 patients without cancer. Cyclosporine therapy and excretory allograft function did not affect marker concentration; impaired liver function was associated with significantly elevated AFP, CA19-9, CA125, and CA15-3 levels. In 43 patients with malignancies the sensitivity of the markers ranged between 0.2 (CEA) and 1 (CA 125, CA 15-3). We therefore conclude that routine screening of the transplant population with serum tumor markers is not useful because of the low sensitivity and specificity of these tests.
The Saccharomyces cerevisiae gene TOR2 encodes a putative phosphatidylinositol kinase that has two essential functions. One function is redundant with TOR1, a TOR2 homolog, and is required for signaling translation initiation and early G1 progression. The second essential function is unique to TOR2. Here we report that loss of the TOR2-unique function disrupts polarized distribution of the actin cytoskeleton. A screen for dosage suppressors of a dominant negative TOR2 allele identified TCP20/CCT6, encoding a subunit of the cytosolic chaperonin TCP-1 that is involved in the biogenesis of actin structures. Overexpression of TCP20 restores growth and polarized distribution of the actin cytoskeleton in a tor2 mutant. TCP20 overexpression does not restore growth in a tor1 tor2 double mutant. We suggest that the unique function of the phosphatidylinositol kinase homolog TOR2 is required for signaling organization of the actin cytoskeleton during the cell cycle. TOR2, via its two functions, may thus integrate temporal and spatial control of cell growth.
The CST20 gene of Candida albicans was cloned by functional complementation of a deletion of the STE20 gene in Saccharomyces cerevisiae. CST20 encodes a homolog of the Ste20p/p65PAK family of protein kinases. Colonies of C. albicans cells deleted for CST20 revealed defects in the lateral formation of mycelia on synthetic solid "Spider" media. However, hyphal development was not impaired in some other media. A similar phenotype was caused by deletion of HST7, encoding a functional homolog of the S. cerevisiae Ste7p protein kinase. Overexpression of HST7 partially complemented the deletion of CST20. Cells deleted for CST20 were less virulent in a mouse model for systemic candidiasis. Our results suggest that more than one signaling pathway can trigger hyphal development in C. albicans, one of which has a protein kinase cascade that is analogous to the mating response pathway in S. cerevisiae and might have become adapted to the control of mycelial formation in asexual C. albicans.
Tyrosinase is one of the key enzymes in mammalian melanin synthesis. The pigment is produced in two different cell types: the pigmented epithelial cell of the retina, and the melanocyte, a cell of neural-crest origin. We recently showed that a fusion gene between regulatory sequences of tyrosinase gene (tyr) and the beta-galactosidase gene (lacZ), when introduced into transgenic mice, resulted in embryonic expression in presumptive pigment cells but also in cells populations along the entire neural tube. This expression in the developing brain was striking, and we therefore asked whether this would still be detectable after birth. Transgenic mice carrying the tyr-lacZ fusion gene showed beta-galactosidase expression in adult brain. On Western blots, we detected tyrosinase-specific bands of 65-68 kDa in brain and eye. Using an affinity-purified antibody, we showed that detection of tyrosinase is specific and competed off by the presence of the cognate tyrosinase-derived peptide. However, neither tyrosine hydroxylase nor Dopa oxidase activity were detected in protein extracts of brain. We therefore suggest that tyrosinase is present in brain but either not functional or catalyzing different reactions compared to pigment cells.
We have previously described the rat liver resealed nuclear envelope model system for the study of the selective import of nuclear proteins, and the export of poly(A)-containing mRNA [Riedel, N., Bachmann, M., Richter, H. & Fasold, H. (1987) Proc. Natl Acad. Sci. USA 83, 3540-3544]. The vesicles still respond to the importin-ATP signal for the uptake of nuclear-location-sequence (NLS)-carrying proteins. During the preparation of the vesicles and extraction of the chromatin from nuclei in cold hypotonic heparin solution, ribosomal subunits may be introduced into these envelopes, and after resealing remain stably included. Efflux from the resealed nuclear envelopes is effected by a cytoplasmatic protein fraction, and strongly enhanced in the presence of ATP. The heterogeneous nuclear RNP (hnRNP) A1, the components of importin, or GTP showed no influence on this export. The ATP-dependent efflux of mRNA is not affected by these cytoplasmic proteins in this model system.
The organization of the motor nuclei of the glossopharyngeal, vagal, occipital, first spinal and second spinal nerves of Typhlonectes natans (Amphibia: Gymnophiona: Caeciliaidae: Typhlonectinae) was studied by using horseradish peroxidase reaction staining. Each nucleus has discrete patterns of cytoarchitecture and of topography. Nuclei are elongate and some overlap anteroposteriorly. The brainstem is elongate, with no distinct demarcation of brainstem from spinal cord. The occipital nerve emerges through a separate foramen from that for the vagus and glossopharyngeal nerves in the species studied, is distinct from both, and its nucleus is more similar to spinal nuclei in cytoarchitecture. The occipital nerve fuses with spinal nerves 1 and 2 to contribute to the hypoglossal trunk. A spinal accessory nerve is absent.